牛体细胞克隆中异常重编程的分析及提高重编程效率的研究
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摘要
体细胞克隆技术（也称为体细胞核移植技术）具有重要的理论研究价值和生产实践价值，可应用于治疗性克隆、高价值药用蛋白的生产、抗病转基因家畜的生产、频临灭绝品种的保护、优良品种家畜的扩增繁殖、人类器官移植和疾病模型的构建等研究。但至今体细胞克隆的效率仍然不高，大量体细胞克隆胎儿在附植期或围产期死亡，出生存活的克隆动物也表现各种发育异常。目前认为，体细胞克隆效率低下的主要原因是供体细胞核不能被卵胞质完全的重编程。本文研究了体细胞克隆动物发育异常和死亡的重编程机理，以及探索通过促进重编程来提高体细胞克隆效率的方法，主要研究的内容和结果如下：
1.在发育异常体细胞克隆牛各组织上分析多个印迹基因的表达和DNA甲基化水平。巨胎症死亡组体细胞克隆牛的体重、胎盘重和单个胎盘子叶重都显著性高于对照组，但胎盘子叶数显著少于对照组。印迹基因XIST、PEG3和IGF2在巨胎症死亡组克隆牛的胎盘等多个组织上表达水平显著高于对照组；而印迹基因H19和IGF2R在巨胎症死亡组克隆牛的胎盘等多个组织上的表达水平显著低于对照组。H19甲基化差异区（DMR）的DNA甲基化水平在巨胎症死亡组牛胎盘等多个组织上显著高于对照组，呈现异常的超甲基化修饰；而XIST DMR和IGF2R DMR的DNA甲基化水平在巨胎症死亡组牛的胎盘等多个组织上显著低于对照组。体细胞克隆中这些异常的重编程（印迹基因的表达和DNA甲基化水平异常）可能和体细胞克隆牛发育异常以及死亡相关。
2.用深度测序技术高通量分析死亡体细胞克隆牛胎盘（克隆组）和正常繁殖生产牛胎盘（对照组）的差异基因表达谱、microRNA信息和全基因组甲基化信息，研究体细胞克隆牛死亡的分子机理。
（1）用RNA-seq (Q)深度测序技术高通量分析克隆组与对照组胎盘的基因表达谱，结果发现相比对照组，克隆组胎盘上有664个基因上调，有1948个基因下调。对这些差异基因进行GO显著性富集分析，发现分子功能上的催化活性、细胞位置上的组织相容性复合体及细胞表面是差异基因显著富集的项。在参与的生物过程上，差异基因有13个显著富集的项，其中大部分项都和免疫相关。差异表达基因显著富集的通路一共有25条，其中14条通路和免疫相关。
（2）用small RNA-seq深度测序技术高通量分析克隆组与对照组胎盘的microRNA信息。在克隆组和对照组胎盘上分别鉴定出了328种和344种已知的成熟microRNA，并发现169种牛的候选新microRNA。对照组和克隆组间共有135个表达显著差异的已知microRNA，其中克隆组有18个已知microRNA的表达上调，117个已知microRNA下调。两样品间有49个表达显著性差异的候选新microRNA，其中克隆组有35个microRNA的表达上调，有14个microRNA下调。
（3）用MeDIP-seq深度测序技术高通量分析克隆组与对照组胎盘上全基因组水平的DNA甲基化信息。本研究首次绘制出反刍动物（牛）的全基因组水平的DNA甲基化图谱。总体上，牛的全基因甲基化模式和其他物种动物和植物的相似。DNA甲基化主要富集在基因内（特别是内含子）和重复序列，而转录起始位点和转录终止位点的DNA甲基化水平较低。牛上大部分CpG岛为非甲基化状态。两样品间有大量差异甲基化水平的基因。共发现37191个CpG岛，甲基化的CpG岛在对照组和克隆租上分别有7482个和5461个。基因表达水平和甲基化水平反相关，转录起始位点附近更为显著，说明启动子甲基化修饰调控基因转录。
3.牛体细胞克隆胚胎上存在异常的重编程。多个基因位点在牛克隆胚胎上存在异常的甲基化修饰，XIST、OCT4、SOX2、NANOG、Rex1和Fgf4基因5’端区域的DMR的甲基化水平在牛体细胞克隆囊胚上都显著低于对照组体外受精囊胚。XIST在体细胞克隆囊胚上的表达水平显著高于对照组体外受精囊胚。H3K27me3在牛体细胞克隆囊胚上的表达异常。
4.用基因芯片高通量分析克隆效率高的细胞系获得的克隆囊胚（高效克隆组组）、克隆效率低下的细胞系获得的克隆囊胚（低效克隆组）以及孤雌囊胚三种类型的囊胚和体外受精囊胚之间的差异基因表达谱。相比体外受精组囊胚，TCF7、DGCR8、SENP7、DNMT3B、Vimentin、IFI6、EFNA2、F5、IRAK1、PRICKLE1、TNFRSF1A、ARG2和NEK6等基因在低效克隆组囊胚上表达异常，但在高效克隆组囊胚上表达正常。这些基因的异常表达可能与低效克隆组细胞系克隆效率低下有关。孤雌囊胚和体外受精囊胚间有240个显著性差异基因。PEG3和SNRPN等多个父源表达的印迹基因在孤雌囊胚上异常下调。
5.分析亮甲酚蓝（BCB）筛选不同核重编程能力的卵母细胞。结果显示用BCB筛选出的不同生长期卵母细胞具有不同的核重编程能力。来自生长完全的卵母细胞(finished growth phase)的牛体细胞克隆胚胎（BCB+）的卵裂率、囊胚发育率、以及移植后胚胎妊娠率和出生率都显著高于来自生长中的卵母细胞(growing oocytes)的克隆胚胎（BCB），说明生长完全的卵母细胞能更好地支持牛克隆胚胎体外和体内发育。BCB+组克隆胚胎上组蛋白乙酰化水平（AcH3K9和AcH3K18）以及H3K4位点的组蛋白甲基化水平高于BCB克隆胚胎，BCB+组克隆胚胎的胚胎质量（胚胎细胞数和胚胎凋亡率）也显著高于BCB克隆胚胎。BCB筛选的不同生长期的卵母细胞也影响克隆胚胎的基因表达。通过BCB筛选出的生长完全的卵母细胞具有更高的体细胞核的重编程能力，将其用于牛体细胞核移植，可提高牛体细胞克隆效率。
6.分析表观修饰药物组蛋白去乙酰化酶抑制剂Oxamflatin对体细胞克隆胚胎的重编程的影响。结果发现1μM Oxamflatin处理牛重构胚12h可提高牛克隆胚胎的AcH3K9和AcH3K18组蛋白乙酰化水平和H3K4me2组蛋白甲基化水平，下调H3K9me3组蛋白甲基化水平，降低体细胞克隆囊胚期胚胎上satellite I的DNA甲基化水平，提高克隆胚胎的质量（胚胎细胞数和胚胎凋亡率），改变克隆胚胎上基因的表达，促进牛体细胞克隆胚胎的体外发育。说明组蛋白去乙酰化酶抑制剂Oxamflatin可促进体细胞核的重编程和克隆胚胎的质量，对牛体细胞克隆胚胎的发育有显著的促进作用。
7.相比体外受精囊胚，TCF7、DGCR8、SENP7、DNMT3B、Vimentin、IFI6、EFNA2、F5、IRAK1、PRICKLE1、TNFRSF1A、ARG2、NEK6、OCT4、NANOG、SOX2、CDX2、XIST和IGF2R这些基因在克隆囊胚上表达正常的细胞系作为核供体获得的克隆胚胎比两个异常表达组的细胞系（异常表达组1是上述4.中的低效克隆组中三株已知遗传背景差的细胞系，用于供体细胞后，在克隆囊胚上TCF7、DGCR8、SENP7、DNMT3B、Vimentin、IFI6、EFNA2、F5、IRAK1、PRICKLE1、TNFRSF1A、ARG2和NEK6等大部分基因表达异常；异常表达组2是三株细胞系，用于供体细胞后，在克隆囊胚上OCT4、NANOG、SOX2、CDX2、XIST和IGF2R等几个多能性基因和印迹基因大部分表达异常）获得的克隆胚胎具有更高的体外和体内发育能力，其克隆效率显著高于两个异常表达组。依据这些基因在克隆囊胚上的表达是否正常可以作为筛选供体细胞系的依据。
本研究发现牛体细胞克隆中存在异常的重编程，表现为早期胚胎上有大量异常表达的基因、异常的DNA甲基化修饰和组蛋白修饰以及新生克隆牛上有大量异常表达的基因、microRNAs和异常的DNA甲基化修饰等。通过筛选易于重编程的供体细胞系、筛选核重编程能力较强的卵母细胞以及通过表观遗传修饰药物处理克隆胚胎，可提高体细胞克隆中的重编程效率，进而提高体细胞克隆效率。
Somatic cloning, also known as somatic cell nuclear transfer (SCNT), is apromising technology with potential applications in therapeutic cloning, producingvaluable recombinant proteins, breeding disease-resistant transgenic livestock, speciespreservation, livestock propagation, man xenotransplantation, and disease models.The cloning efficiency, however, remains low, which is a significant barrier to thewidespread use of such a promising technology. It is generally believed that the lowcloning efficiency is mostly attributed to aberrant nuclear reprogramming of the donorcell by oocytes. In the present study, the pathogenic mechanisms of developmentalabnormity in SCNT cattle were analyzed, and then how to improve the somaticcloning efficiency through enhancing nuclear reprogramming was analyzed.
1. The expression and DNA methylation status of imprinted genes in various tissuesfrom deceased cloned calves were analyzed using Quantitative RT-PCR (qRT-PCR),Bisulfite Sequencing PCR (BSP) and Combined Bisulfite Restriction Analysis(COBRA). The results showed that fetal weigh, placental weight and meanplacentome weight were larger, but the number of placentomes was smaller in thedeceased calves with Large Offspring Syndrome (LOS group) compared with thecontrol group. The XIST, PEG3and IGF2were significantly over-expressed inmultiple tissues (e.g. placenta) from the LOS group, whereas expression of H19andIGF2R was significantly reduced in multiple tissues (e.g. placenta) from the LOSgroup compared with controls. In multiple tissues (e.g. placenta) from the LOS group,H19DMR was significantly hypermethylated, but XIST DMR and IGF2R ICR weresignificantly hypomethylated compared with controls. We inferred that abnormalexpression of the imprinted genes in deceased calves could be associated with alteredDNA methylation levels at the DMRs of these imprinted genes. These alterationscould result from aberrant epigenetic nuclear reprogramming during SCNT and maydisrupt normal developmental regulation of placenta and fetus, which may result indevelopmental insufficiencies and ultimately fetal or perinatal death in cloned transgenic calves.
2. The pathogenic mechanism of developmental abnormity and death in SCNTcattle was analyzed in placenta from deceased cloned calves (SCNT group) andnormally produced female calves (control group) using Solexa sequencing.
(1) Gene expression difference analysis between SCNT and control sample usingRNA-seq (Q) HiSeq high-throughput sequencing revealed664up-regulated and1948down-regulated genes in SCNT group compared with control group. To investigatethe function distribution of differentially expressed genes (DEGs), we performed theGene Ontology (GO) enrichment analysis for the DEGs. DEGs were enriched in thefunctions of catalytic activity. DEGs were enriched in the cellular component of MHCprotein complex and cell surface. DEGs were enriched in the biological process of13GO term, most of them were related with immune system, for instance, immunesystem process, antigen processing and presentation of peptide antigen, immuneresponse, positive regulation of immune system process, and activation of immuneresponse, etc. Pathway enrichment analysis of DEGs showed that25Pathway weresignificantly enriched pathway, and most of them were related with immune system,for instance, Graft-versus-host disease, Allograft rejection, Antigen processing andpresentation, NOD and Toll-like receptor signaling pathway, Leukocytetransendothelial migration, and Autoimmune thyroid disease, etc.
(2) The microRNA information was analyzed by small RNA-seq in SCNT andcontrol placentas.328and344unique known bovine microRNAs were identified inSCNT and control placentas, respectively.169unique predicted novel bovinemicroRNAs were found in bovine placentas.135unique known microRNAs weredifferentially expressed between two samples,18microRNAs were up-regulated and117microRNAs were down-regulated in SCNT placentas compared with controls.49unique novel microRNAs were differentially expressed between two samples,35microRNAs were up-regulated and14microRNAs were down-regulated in SCNTplacentas compared with controls.
(3) The genome-wide patterns of DNA methylation were analyzed by MeDIP-seqin SCNT and control placentas. The genome-wide map of DNA methylation inruminants (cattle in this study) was, for the fist time, reported in the present study.Generally, cattle display analogous methylation pattern with that of other animals andplants. DNA methylation is enriched in the gene body regions (especially introns) andthe repetitive sequences, and depleted in the transcription start site (TSS) and the transcription termination site (TTS). Most of the CpG islands in the cattle genomewere kept in unmethylated state. There were many differentially methylated genesbetween SCNT and control placentas.37,191CpG islands were found in bovineplacentas.7,482and5,461methylated CpG islands were found in control and SCNTplacentas, respectively. The DNA methylation level of promoters was negativelycorrelated with the gene expression level, indicating its suppressive role in regulatinggene transcription.
3. Aberrant reprogramming was found in bovine cloned embryos. The XIST, OCT4,SOX2, NANOG, Rex1, and Fgf4were significantly hypomethylated in SCNTblastocysts compared with IVF blastocysts. The XIST was significantlyover-expressed in SCNT blastocysts compared with IVF blastocysts. The expressionof H3K27me3was aberrant in SCNT blastocysts compared with IVF blastocysts.
4. Global gene expression profilings were analyzed in SCNT blastocysts from celllines with high cloning efficiency (high efficiency group), SCNT blastocysts from celllines with low cloning efficiency (low efficiency group), parthenogenetic blastocysts(parthenogenesis group), and IVF blastocysts (IVF grpoup). TCF7, DGCR8, SENP7,DNMT3B, Vimentin, IFI6, EFNA2, F5, IRAK1, PRICKLE1, TNFRSF1A, ARG2,NEK6, and other genes were abnormally expressed in low efficiency group, whichnormally expressed in high efficiency group, compared with the IVF grpoup. Therewere240differentially expressed genes between parthenogenesis group and IVFgrpoup. Expression of PEG3and SNRPN, the paternally expressed imprinted genes,were significantly reduced in parthenogenetic blastocysts compared with the IVFblastocysts.
5. The differential bovine oocytes with different nuclear reprogramming capacitywere selected by Brilliant cresyl blue (BCB) staining. The results showed that oocytesof various growth stage selected by BCB staining yield different nuclearreprogramming capacity. The cloned embryos developed from oocytes of finishedgrowth phase (BCB+) showed higher cleavage rate, blastocyst rate, pregnancy rateand full term development rate than these developed from growing oocytes (BCB).Oocytes of finished growth phase support higher developmental competence ofbovine cloned embryos in vitro and in vivo. The global acetylation levels of H3K9and H3K18and the global methylation levels of H3K4in BCB+embryos at thetwo-cell stage were higher than in BCB embryos. BCB+embryos generated moretotal cells, trophectoderm (TE) cells, and inner cell mass (ICM) cells, and fewer apoptotic cells than BCB embryos. The gene expressions in BCB+and BCB blastocysts were also different. These results strongly suggest that BCB+oocytes(finished growth phase) have a higher nuclear reprogramming capacity, and that BCBstaining can be used to select developmentally competent oocytes for nuclear transfer.
6. The effects of Oxamflatin, a novel HDACi, on the nuclear reprogramming anddevelopment of bovine SCNT embryos in vitro were analyzed. The results showedthat Oxamflatin treatment (the SCNT embryos treated with1μM Oxamflatinpost-ionomycin for12h) increased the global acetylation levels of H3K9and H3K18and the global methylation levels of H3K4, but decreased the the global methylationlevels of H3K9, reduced the DNA methylation level of satellite I in SCNT blastocysts,increased total and inner cell mass (ICM) cell numbers and the ratio ofICM:trophectoderm (TE) cells, reduced the rate of apoptosis in SCNT blastocysts,modified gene expression and significantly enhanced the development of bovineSCNT embryos in vitro. The study showed that Oxamflatin modifies epigenetic statusand gene expression, increases blastocyst quality, and subsequently enhances thenuclear reprogramming and developmental potential of SCNT embryos.
7. The SCNT embryos derived from cell lines of normal expression group (TCF7,DGCR8, SENP7, DNMT3B, Vimentin, IFI6, EFNA2, F5, IRAK1, PRICKLE1,TNFRSF1A, ARG2, NEK6, OCT4, NANOG, SOX2, CDX2, XIST, and IGF2R werenormally expressed in SCNT blastocysts derived from these cell lines compare withIVF blastocysts) showed higher blastocyst rate, pregnancy rate and full termdevelopment rate than SCNT embryos derived from cell lines of two abnormalexpression groups (abnormal expression group1: low efficiency group in4.above-mentioned, TCF7, DGCR8, SENP7, DNMT3B, Vimentin, IFI6, EFNA2, F5,IRAK1, PRICKLE1, TNFRSF1A, ARG2, NEK6, and other genes were abnormallyexpressed in SCNT blastocysts derived from these cell lines compare with IVFblastocysts; abnormal expression group2: OCT4, NANOG, SOX2, CDX2, XIST andIGF2R were abnormally expressed in SCNT blastocysts derived from these cell linescompare with IVF blastocysts). Expression profiling analysis of TCF7, DGCR8,SENP7, DNMT3B, Vimentin, IFI6, EFNA2, F5, IRAK1, PRICKLE1, TNFRSF1A,ARG2, NEK6, OCT4, NANOG, SOX2, CDX2, XIST, and IGF2R in cloned embryoscould be as a method to select good donor cell lines.
Aberrant reprogramming, including alterations in gene expressions, DNAmethylation status of genes, histone modifications, and microRNAs in cloned embryos or cloned calves, was found during bovine somatic cloning, which maysubsequently result in developmental insufficiencies and ultimately fetal or perinataldeath in cloned calves. The reprogramming efficiency and even somatic cloningefficiency could be enhanced by selecting good donor cells, selecting oocytes withhigher nuclear reprogramming capacity and the treatments of cloned embryos withepigenetic drugs.
1.在发育异常体细胞克隆牛各组织上分析多个印迹基因的表达和DNA甲基化水平。巨胎症死亡组体细胞克隆牛的体重、胎盘重和单个胎盘子叶重都显著性高于对照组，但胎盘子叶数显著少于对照组。印迹基因XIST、PEG3和IGF2在巨胎症死亡组克隆牛的胎盘等多个组织上表达水平显著高于对照组；而印迹基因H19和IGF2R在巨胎症死亡组克隆牛的胎盘等多个组织上的表达水平显著低于对照组。H19甲基化差异区（DMR）的DNA甲基化水平在巨胎症死亡组牛胎盘等多个组织上显著高于对照组，呈现异常的超甲基化修饰；而XIST DMR和IGF2R DMR的DNA甲基化水平在巨胎症死亡组牛的胎盘等多个组织上显著低于对照组。体细胞克隆中这些异常的重编程（印迹基因的表达和DNA甲基化水平异常）可能和体细胞克隆牛发育异常以及死亡相关。
2.用深度测序技术高通量分析死亡体细胞克隆牛胎盘（克隆组）和正常繁殖生产牛胎盘（对照组）的差异基因表达谱、microRNA信息和全基因组甲基化信息，研究体细胞克隆牛死亡的分子机理。
（1）用RNA-seq (Q)深度测序技术高通量分析克隆组与对照组胎盘的基因表达谱，结果发现相比对照组，克隆组胎盘上有664个基因上调，有1948个基因下调。对这些差异基因进行GO显著性富集分析，发现分子功能上的催化活性、细胞位置上的组织相容性复合体及细胞表面是差异基因显著富集的项。在参与的生物过程上，差异基因有13个显著富集的项，其中大部分项都和免疫相关。差异表达基因显著富集的通路一共有25条，其中14条通路和免疫相关。
（2）用small RNA-seq深度测序技术高通量分析克隆组与对照组胎盘的microRNA信息。在克隆组和对照组胎盘上分别鉴定出了328种和344种已知的成熟microRNA，并发现169种牛的候选新microRNA。对照组和克隆组间共有135个表达显著差异的已知microRNA，其中克隆组有18个已知microRNA的表达上调，117个已知microRNA下调。两样品间有49个表达显著性差异的候选新microRNA，其中克隆组有35个microRNA的表达上调，有14个microRNA下调。
（3）用MeDIP-seq深度测序技术高通量分析克隆组与对照组胎盘上全基因组水平的DNA甲基化信息。本研究首次绘制出反刍动物（牛）的全基因组水平的DNA甲基化图谱。总体上，牛的全基因甲基化模式和其他物种动物和植物的相似。DNA甲基化主要富集在基因内（特别是内含子）和重复序列，而转录起始位点和转录终止位点的DNA甲基化水平较低。牛上大部分CpG岛为非甲基化状态。两样品间有大量差异甲基化水平的基因。共发现37191个CpG岛，甲基化的CpG岛在对照组和克隆租上分别有7482个和5461个。基因表达水平和甲基化水平反相关，转录起始位点附近更为显著，说明启动子甲基化修饰调控基因转录。
3.牛体细胞克隆胚胎上存在异常的重编程。多个基因位点在牛克隆胚胎上存在异常的甲基化修饰，XIST、OCT4、SOX2、NANOG、Rex1和Fgf4基因5’端区域的DMR的甲基化水平在牛体细胞克隆囊胚上都显著低于对照组体外受精囊胚。XIST在体细胞克隆囊胚上的表达水平显著高于对照组体外受精囊胚。H3K27me3在牛体细胞克隆囊胚上的表达异常。
4.用基因芯片高通量分析克隆效率高的细胞系获得的克隆囊胚（高效克隆组组）、克隆效率低下的细胞系获得的克隆囊胚（低效克隆组）以及孤雌囊胚三种类型的囊胚和体外受精囊胚之间的差异基因表达谱。相比体外受精组囊胚，TCF7、DGCR8、SENP7、DNMT3B、Vimentin、IFI6、EFNA2、F5、IRAK1、PRICKLE1、TNFRSF1A、ARG2和NEK6等基因在低效克隆组囊胚上表达异常，但在高效克隆组囊胚上表达正常。这些基因的异常表达可能与低效克隆组细胞系克隆效率低下有关。孤雌囊胚和体外受精囊胚间有240个显著性差异基因。PEG3和SNRPN等多个父源表达的印迹基因在孤雌囊胚上异常下调。
5.分析亮甲酚蓝（BCB）筛选不同核重编程能力的卵母细胞。结果显示用BCB筛选出的不同生长期卵母细胞具有不同的核重编程能力。来自生长完全的卵母细胞(finished growth phase)的牛体细胞克隆胚胎（BCB+）的卵裂率、囊胚发育率、以及移植后胚胎妊娠率和出生率都显著高于来自生长中的卵母细胞(growing oocytes)的克隆胚胎（BCB），说明生长完全的卵母细胞能更好地支持牛克隆胚胎体外和体内发育。BCB+组克隆胚胎上组蛋白乙酰化水平（AcH3K9和AcH3K18）以及H3K4位点的组蛋白甲基化水平高于BCB克隆胚胎，BCB+组克隆胚胎的胚胎质量（胚胎细胞数和胚胎凋亡率）也显著高于BCB克隆胚胎。BCB筛选的不同生长期的卵母细胞也影响克隆胚胎的基因表达。通过BCB筛选出的生长完全的卵母细胞具有更高的体细胞核的重编程能力，将其用于牛体细胞核移植，可提高牛体细胞克隆效率。
6.分析表观修饰药物组蛋白去乙酰化酶抑制剂Oxamflatin对体细胞克隆胚胎的重编程的影响。结果发现1μM Oxamflatin处理牛重构胚12h可提高牛克隆胚胎的AcH3K9和AcH3K18组蛋白乙酰化水平和H3K4me2组蛋白甲基化水平，下调H3K9me3组蛋白甲基化水平，降低体细胞克隆囊胚期胚胎上satellite I的DNA甲基化水平，提高克隆胚胎的质量（胚胎细胞数和胚胎凋亡率），改变克隆胚胎上基因的表达，促进牛体细胞克隆胚胎的体外发育。说明组蛋白去乙酰化酶抑制剂Oxamflatin可促进体细胞核的重编程和克隆胚胎的质量，对牛体细胞克隆胚胎的发育有显著的促进作用。
7.相比体外受精囊胚，TCF7、DGCR8、SENP7、DNMT3B、Vimentin、IFI6、EFNA2、F5、IRAK1、PRICKLE1、TNFRSF1A、ARG2、NEK6、OCT4、NANOG、SOX2、CDX2、XIST和IGF2R这些基因在克隆囊胚上表达正常的细胞系作为核供体获得的克隆胚胎比两个异常表达组的细胞系（异常表达组1是上述4.中的低效克隆组中三株已知遗传背景差的细胞系，用于供体细胞后，在克隆囊胚上TCF7、DGCR8、SENP7、DNMT3B、Vimentin、IFI6、EFNA2、F5、IRAK1、PRICKLE1、TNFRSF1A、ARG2和NEK6等大部分基因表达异常；异常表达组2是三株细胞系，用于供体细胞后，在克隆囊胚上OCT4、NANOG、SOX2、CDX2、XIST和IGF2R等几个多能性基因和印迹基因大部分表达异常）获得的克隆胚胎具有更高的体外和体内发育能力，其克隆效率显著高于两个异常表达组。依据这些基因在克隆囊胚上的表达是否正常可以作为筛选供体细胞系的依据。
本研究发现牛体细胞克隆中存在异常的重编程，表现为早期胚胎上有大量异常表达的基因、异常的DNA甲基化修饰和组蛋白修饰以及新生克隆牛上有大量异常表达的基因、microRNAs和异常的DNA甲基化修饰等。通过筛选易于重编程的供体细胞系、筛选核重编程能力较强的卵母细胞以及通过表观遗传修饰药物处理克隆胚胎，可提高体细胞克隆中的重编程效率，进而提高体细胞克隆效率。
Somatic cloning, also known as somatic cell nuclear transfer (SCNT), is apromising technology with potential applications in therapeutic cloning, producingvaluable recombinant proteins, breeding disease-resistant transgenic livestock, speciespreservation, livestock propagation, man xenotransplantation, and disease models.The cloning efficiency, however, remains low, which is a significant barrier to thewidespread use of such a promising technology. It is generally believed that the lowcloning efficiency is mostly attributed to aberrant nuclear reprogramming of the donorcell by oocytes. In the present study, the pathogenic mechanisms of developmentalabnormity in SCNT cattle were analyzed, and then how to improve the somaticcloning efficiency through enhancing nuclear reprogramming was analyzed.
1. The expression and DNA methylation status of imprinted genes in various tissuesfrom deceased cloned calves were analyzed using Quantitative RT-PCR (qRT-PCR),Bisulfite Sequencing PCR (BSP) and Combined Bisulfite Restriction Analysis(COBRA). The results showed that fetal weigh, placental weight and meanplacentome weight were larger, but the number of placentomes was smaller in thedeceased calves with Large Offspring Syndrome (LOS group) compared with thecontrol group. The XIST, PEG3and IGF2were significantly over-expressed inmultiple tissues (e.g. placenta) from the LOS group, whereas expression of H19andIGF2R was significantly reduced in multiple tissues (e.g. placenta) from the LOSgroup compared with controls. In multiple tissues (e.g. placenta) from the LOS group,H19DMR was significantly hypermethylated, but XIST DMR and IGF2R ICR weresignificantly hypomethylated compared with controls. We inferred that abnormalexpression of the imprinted genes in deceased calves could be associated with alteredDNA methylation levels at the DMRs of these imprinted genes. These alterationscould result from aberrant epigenetic nuclear reprogramming during SCNT and maydisrupt normal developmental regulation of placenta and fetus, which may result indevelopmental insufficiencies and ultimately fetal or perinatal death in cloned transgenic calves.
2. The pathogenic mechanism of developmental abnormity and death in SCNTcattle was analyzed in placenta from deceased cloned calves (SCNT group) andnormally produced female calves (control group) using Solexa sequencing.
(1) Gene expression difference analysis between SCNT and control sample usingRNA-seq (Q) HiSeq high-throughput sequencing revealed664up-regulated and1948down-regulated genes in SCNT group compared with control group. To investigatethe function distribution of differentially expressed genes (DEGs), we performed theGene Ontology (GO) enrichment analysis for the DEGs. DEGs were enriched in thefunctions of catalytic activity. DEGs were enriched in the cellular component of MHCprotein complex and cell surface. DEGs were enriched in the biological process of13GO term, most of them were related with immune system, for instance, immunesystem process, antigen processing and presentation of peptide antigen, immuneresponse, positive regulation of immune system process, and activation of immuneresponse, etc. Pathway enrichment analysis of DEGs showed that25Pathway weresignificantly enriched pathway, and most of them were related with immune system,for instance, Graft-versus-host disease, Allograft rejection, Antigen processing andpresentation, NOD and Toll-like receptor signaling pathway, Leukocytetransendothelial migration, and Autoimmune thyroid disease, etc.
(2) The microRNA information was analyzed by small RNA-seq in SCNT andcontrol placentas.328and344unique known bovine microRNAs were identified inSCNT and control placentas, respectively.169unique predicted novel bovinemicroRNAs were found in bovine placentas.135unique known microRNAs weredifferentially expressed between two samples,18microRNAs were up-regulated and117microRNAs were down-regulated in SCNT placentas compared with controls.49unique novel microRNAs were differentially expressed between two samples,35microRNAs were up-regulated and14microRNAs were down-regulated in SCNTplacentas compared with controls.
(3) The genome-wide patterns of DNA methylation were analyzed by MeDIP-seqin SCNT and control placentas. The genome-wide map of DNA methylation inruminants (cattle in this study) was, for the fist time, reported in the present study.Generally, cattle display analogous methylation pattern with that of other animals andplants. DNA methylation is enriched in the gene body regions (especially introns) andthe repetitive sequences, and depleted in the transcription start site (TSS) and the transcription termination site (TTS). Most of the CpG islands in the cattle genomewere kept in unmethylated state. There were many differentially methylated genesbetween SCNT and control placentas.37,191CpG islands were found in bovineplacentas.7,482and5,461methylated CpG islands were found in control and SCNTplacentas, respectively. The DNA methylation level of promoters was negativelycorrelated with the gene expression level, indicating its suppressive role in regulatinggene transcription.
3. Aberrant reprogramming was found in bovine cloned embryos. The XIST, OCT4,SOX2, NANOG, Rex1, and Fgf4were significantly hypomethylated in SCNTblastocysts compared with IVF blastocysts. The XIST was significantlyover-expressed in SCNT blastocysts compared with IVF blastocysts. The expressionof H3K27me3was aberrant in SCNT blastocysts compared with IVF blastocysts.
4. Global gene expression profilings were analyzed in SCNT blastocysts from celllines with high cloning efficiency (high efficiency group), SCNT blastocysts from celllines with low cloning efficiency (low efficiency group), parthenogenetic blastocysts(parthenogenesis group), and IVF blastocysts (IVF grpoup). TCF7, DGCR8, SENP7,DNMT3B, Vimentin, IFI6, EFNA2, F5, IRAK1, PRICKLE1, TNFRSF1A, ARG2,NEK6, and other genes were abnormally expressed in low efficiency group, whichnormally expressed in high efficiency group, compared with the IVF grpoup. Therewere240differentially expressed genes between parthenogenesis group and IVFgrpoup. Expression of PEG3and SNRPN, the paternally expressed imprinted genes,were significantly reduced in parthenogenetic blastocysts compared with the IVFblastocysts.
5. The differential bovine oocytes with different nuclear reprogramming capacitywere selected by Brilliant cresyl blue (BCB) staining. The results showed that oocytesof various growth stage selected by BCB staining yield different nuclearreprogramming capacity. The cloned embryos developed from oocytes of finishedgrowth phase (BCB+) showed higher cleavage rate, blastocyst rate, pregnancy rateand full term development rate than these developed from growing oocytes (BCB).Oocytes of finished growth phase support higher developmental competence ofbovine cloned embryos in vitro and in vivo. The global acetylation levels of H3K9and H3K18and the global methylation levels of H3K4in BCB+embryos at thetwo-cell stage were higher than in BCB embryos. BCB+embryos generated moretotal cells, trophectoderm (TE) cells, and inner cell mass (ICM) cells, and fewer apoptotic cells than BCB embryos. The gene expressions in BCB+and BCB blastocysts were also different. These results strongly suggest that BCB+oocytes(finished growth phase) have a higher nuclear reprogramming capacity, and that BCBstaining can be used to select developmentally competent oocytes for nuclear transfer.
6. The effects of Oxamflatin, a novel HDACi, on the nuclear reprogramming anddevelopment of bovine SCNT embryos in vitro were analyzed. The results showedthat Oxamflatin treatment (the SCNT embryos treated with1μM Oxamflatinpost-ionomycin for12h) increased the global acetylation levels of H3K9and H3K18and the global methylation levels of H3K4, but decreased the the global methylationlevels of H3K9, reduced the DNA methylation level of satellite I in SCNT blastocysts,increased total and inner cell mass (ICM) cell numbers and the ratio ofICM:trophectoderm (TE) cells, reduced the rate of apoptosis in SCNT blastocysts,modified gene expression and significantly enhanced the development of bovineSCNT embryos in vitro. The study showed that Oxamflatin modifies epigenetic statusand gene expression, increases blastocyst quality, and subsequently enhances thenuclear reprogramming and developmental potential of SCNT embryos.
7. The SCNT embryos derived from cell lines of normal expression group (TCF7,DGCR8, SENP7, DNMT3B, Vimentin, IFI6, EFNA2, F5, IRAK1, PRICKLE1,TNFRSF1A, ARG2, NEK6, OCT4, NANOG, SOX2, CDX2, XIST, and IGF2R werenormally expressed in SCNT blastocysts derived from these cell lines compare withIVF blastocysts) showed higher blastocyst rate, pregnancy rate and full termdevelopment rate than SCNT embryos derived from cell lines of two abnormalexpression groups (abnormal expression group1: low efficiency group in4.above-mentioned, TCF7, DGCR8, SENP7, DNMT3B, Vimentin, IFI6, EFNA2, F5,IRAK1, PRICKLE1, TNFRSF1A, ARG2, NEK6, and other genes were abnormallyexpressed in SCNT blastocysts derived from these cell lines compare with IVFblastocysts; abnormal expression group2: OCT4, NANOG, SOX2, CDX2, XIST andIGF2R were abnormally expressed in SCNT blastocysts derived from these cell linescompare with IVF blastocysts). Expression profiling analysis of TCF7, DGCR8,SENP7, DNMT3B, Vimentin, IFI6, EFNA2, F5, IRAK1, PRICKLE1, TNFRSF1A,ARG2, NEK6, OCT4, NANOG, SOX2, CDX2, XIST, and IGF2R in cloned embryoscould be as a method to select good donor cell lines.
Aberrant reprogramming, including alterations in gene expressions, DNAmethylation status of genes, histone modifications, and microRNAs in cloned embryos or cloned calves, was found during bovine somatic cloning, which maysubsequently result in developmental insufficiencies and ultimately fetal or perinataldeath in cloned calves. The reprogramming efficiency and even somatic cloningefficiency could be enhanced by selecting good donor cells, selecting oocytes withhigher nuclear reprogramming capacity and the treatments of cloned embryos withepigenetic drugs.
引文
马晶晶,王勇胜,何小宁,郑月茂,张涌.2010.牛胎儿成纤维细胞β防御素(hBD3)基因转染及转基因克隆胚制备.农业生物技术学报,18(4):707~712
Aguilar A L, Piskol R, Beitzinger M, Zhu J Y, Kruspe D, Aszodi A, Moser M, Englert C, and Meister G.2010. The small RNA expression profile of the developing murine urinary and reproductivesystems. Febs Letters,584(21):4426-4434
Akagi S, Adachi N, Matsukawa K, Kubo M, and Takahashi S.2003. Developmental potential of bovinenuclear transfer embryos and postnatal survival rate of cloned calves produced by two differenttimings of fusion and activation. Molecular Reproduction and Development,66(3):264-272
Al-Katanani Y M, Paula-Lopes F F, and Hansen P J.2002. Effect of season and exposure to heat stress onoocyte competence in Holstein cows. Journal of Dairy Science,85(2):390-396
Allfrey V, Faulkner R, and Mirsky A.1964. Acetylation and methylation of histones and their possible rolein the regulation of RNA synthesis. Proceedings of the National Academy of Sciences of theUnited States of America,51(5):786
Alm H, Torner H, Lohrke B, Viergutz T, Ghoneim I M, and Kanitz W.2005. Bovine blastocystdevelopment rate in vitro is influenced by selection of oocytes by brillant cresyl blue stainingbefore IVM as indicator for glucose-6-phosphate dehydrogenase activity. Theriogenology,63(8):2194-2205
Anderlind C, Spira A, Cardoso W V, and Lü J.2010. miR-129regulates cell proliferation bydownregulating Cdk6expression. Cell Cycle,9(9):1809-1818
Arat S, Gibbons J, Rzucidlo S J, Respess D S, Tumlin M, and Stice S L.2002. In vitro development ofbovine nuclear transfer embryos from transgenic clonal lines of adult and fetal fibroblast cells ofthe same genotype. Biology of Reproduction,66(6):1768-1774
Ariel M, Robinson E, Mccarrey J R, and Cedar H.1995. Gamete-Specific Methylation Correlates withImprinting of the Murine Xist Gene. Nature Genetics,9(3):312-315
Arnold D R, Fortier A L, Lefebvre R, Miglino M A, Pfarrer C, and Smith L C.2008. Placentalinsufficiencies in cloned animals-a workshop report. Placenta,29Suppl A: S108-S110
Aston K I, Li G P, Hicks B A, Sessions B R, Davis A P, Rickords L F, Stevens J R, and White K L.2010.Abnormal Levels of Transcript Abundance of Developmentally Important Genes in Various Stagesof Preimplantation Bovine Somatic Cell Nuclear Transfer Embryos. Cellular Reprogramming,12(1):23-32
Audic S, and Claverie J M.1997. The significance of digital gene expression profiles. Genome Research,7(10):986-995
Baguisi A, Behboodi E, Melican D T, Pollock J S, Destrempes M M, Cammuso C, Williams J L, Nims S D,Porter C A, Midura P, Palacios M J, Ayres S L, Denniston R S, Hayes M L, Ziomek C A, Meade HM, Godke R A, Gavin W G, Overstrom E W, and Echelard Y.1999. Production of goats by somaticcell nuclear transfer. Nature Biotechnology,17(5):456-461
Bartel D P.2004. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell,116(2):281-297
Beard C, Li E, and Jaenisch R.1995. Loss of methylation activates Xist in somatic but not in embryoniccells. Genes Dev,9(19):2325-2334
Bedford M T, and Clarke S G.2009. Protein arginine methylation in mammals: who, what, and why.Molecular Cell,33(1):1-13
Beebe L F S, Mcllfatrick S J, and Nottle M B.2009. Cytochalasin B and Trichostatin A TreatmentPostactivation Improves In Vitro Development of Porcine Somatic Cell Nuclear Transfer Embryos.Cloning and Stem Cells,11(4):477-482
Benjamini Y, and Yekutieli D.2001. The control of the false discovery rate in multiple testing underdependency. Annals of statistics,29(4):1165-1188
Berg D K, Smith C S, Pearton D J, Wells D N, Broadhurst R, Donnison M, and Pfeffer P L.2011.Trophectoderm Lineage Determination in Cattle. Developmental Cell,20(2):244-255
Bermejo-Alvarez P, Ramos-Ibeas P, and Gutierrez-Adan A.2012. Solving the "x" in embryos and stemcells. Stem Cells Dev,21(8):1215-1224
Beyhan Z, Forsberg E J, Eilertsen K J, Kent-First M, and First N L.2007. Gene expression in bovinenuclear transfer embryos in relation to donor cell efficiency in producing live offspring. MolecularReproduction and Development,74(1):18-27
Bhojwani S, Alm H, Torner H, Kanitz W, and Poehland R.2007. Selection of developmentally competentoocytes through brilliant cresyl blue stain enhances blastocyst development rate after bovinenuclear transfer. Theriogenology,67(2):341-345
Bischoff S R, Tsai S, Hardison N, Motsinger-Reif A A, Freking B A, Nonneman D, Rohrer G, andPiedrahita J A.2009. Characterization of Conserved and Nonconserved Imprinted Genes in Swine.Biology of Reproduction,81(5):906-920
Blackwell L, Norris J, Suto C M, and Janzen W P.2008. The use of diversity profiling to characterizechemical modulators of the histone deacetylases. Life Sciences,82(21):1050-1058
Blondin P, Bousquet D, Twagiramungu H, Barnes F, and Sirard M A.2002. Manipulation of folliculardevelopment to produce developmentally competent bovine oocytes. Biology of Reproduction,66(1):38-43
Bock C, Reither S, Mikeska T, Paulsen M, Walter J, and Lengauer T.2005. BiQ analyzer: visualization andquality control for DNA methylation data from bisulfite sequencing. Bioinformatics,21(21):4067-4068
Borden E C, Lindner D, Dreicer R, Hussein M, and Peereboom D.(2000). Second-generation interferonsfor cancer: clinical targets.Seminars in Cancer Biology,10(2):125-144
Bostick M, Kim J K, Esteve P O, Clark A, Pradhan S, and Jacobsen S E.2007. UHRF1plays a role inmaintaining DNA methylation in mammalian cells. Science,317(5845):1760-1764
Brennecke J, Stark A, Russell R B, and Cohen S M.2005. Principles of microRNA-target recognition. PlosBiology,3(3): e85
Bui H T, Wakayama S, Kishigami S, Park K K, Kim J H, Thuan N V, and Wakayama T.2010. Effect oftrichostatin A on chromatin remodeling, histone modifications, DNA replication, andtranscriptional activity in cloned mouse embryos. Biology of Reproduction,83(3):454-63
Buscaglia L E, and Li Y.2011. Apoptosis and the target genes of microRNA-21. Chin J Cancer,30(6):371-80
Campbell K H, McWhir J, Ritchie W A, and Wilmut I.1996. Sheep cloned by nuclear transfer from acultured cell line. Nature,380(6569):64-66
Campbell K H S, Fisher P, Chen W C, Choi I, Kelly R D W, Lee J H, and Xhu J.2007. Somatic cellnuclear transfer: Past, present and future perspectives. Theriogenology,68Suppl1: S214-S231
Carreira-Barbosa F, Concha M L, Takeuchi M, Ueno N, Wilson S W, and Tada M.2003. Prickle1regulatescell movements during gastrulation and neuronal migration in zebrafish. Development,130(17):4037-4046
Castro F, Sharbati S, Rodriguez-Alvarez L, Cox J, Hultschig C, and Einspanier R.2010. MicroRNAexpression profiling of elongated cloned and in vitro-fertilized bovine embryos. Theriogenology,73(1):71-85
Catala M G, Izquierdo D, Uzbekova S, Morato R, Roura M, Romaguera R, Papillier P, and Paramio M T.2011. Brilliant Cresyl Blue stain selects largest oocytes with highest mitochondrial activity,maturation-promoting factor activity and embryo developmental competence in prepubertal sheep.Reproduction,142(4):517-27
Cervera R P, Silvestre M A, Marti N, Garcia-Mengual E, Moreno R, and Stojkovic M.2010. Effects ofdifferent oocyte activation procedures on development and gene expression of porcinepre-implantation embryos. Reproduction in Domestic Animals,45(5): e12-20
Chan J A, Krichevsky A M, and Kosik K S.2005. MicroRNA-21is an antiapoptotic factor in humanglioblastoma cells. Cancer Research,65(14):6029-6033
Chavatte-Palmer P, Heyman Y, Richard C, Monget P, LeBourhis D, Kann G, Chilliard Y, Vignon X, andRenard J.2002a. Clinical, hormonal, and hematologic characteristics of bovine calves derivedfrom nuclei from somatic cells. Biology of Reproduction,66(6):1596-1603
Chen T P, Tsujimoto N, and Li E.2004. The PWWP domain of Dnmt3a and Dnmt3b is required fordirecting DNA methylation to the major satellite repeats at pericentric heterochromatin. Molecularand Cellular Biology,24(20):9048-9058
Cheriyath V, Glaser K B, Waring J F, Baz R, Hussein M A, and Borden E C.2007. G1P3, an IFN-inducedsurvival factor, antagonizes TRAIL-induced apoptosis in human myeloma cells. Journal ofClinical Investigation,117(10):3107-3117
Chesne P, Adenot P G, Viglietta C, Baratte M, Boulanger L, and Renard J P.2002. Cloned rabbits producedby nuclear transfer from adult somatic cells. Nature Biotechnology,20(4):366-369
Chiyomaru T, Enokida H, Tatarano S, Kawahara K, Uchida Y, Nishiyama K, Fujimura L, Kikkawa N, SekiN, and Nakagawa M.2010. miR-145and miR-133a function as tumour suppressors and directlyregulate FSCN1expression in bladder cancer. British Journal of Cancer,102(5):883-891
Cokus S J, Feng S, Zhang X, Chen Z, Merriman B, Haudenschild C D, Pradhan S, Nelson S F, PellegriniM, and Jacobsen S E.2008. Shotgun bisulphite sequencing of the Arabidopsis genome revealsDNA methylation patterning. Nature,452(7184):215-219
Constant F, Guillomot M, Heyman Y, Vignon X, Laigre P, Servely J L, Renard J P, and Chavatte-Palmer P.2006. Large offspring or large placenta syndrome? Morphometric analysis of late gestation bovineplacentomes from somatic nuclear transfer pregnancies complicated by hydrallantois. Biology ofReproduction,75(1):122-130
Cortázar D, Kunz C, Selfridge J, Lettieri T, Saito Y, MacDougall E, Wirz A, Schuermann D, Jacobs A L,and Siegrist F.2011. Embryonic lethal phenotype reveals a function of TDG in maintainingepigenetic stability. Nature,470(7334):419-423
Cortellino S, Xu J, Sannai M, Moore R, Caretti E, Cigliano A, LeáCoz M, Devarajan K, Wessels A, andSoprano D.2011. Thymine DNA glycosylase is essential for active DNA demethylation by linkeddeamination-base excision repair. Cell,146(1):67-79
Costa-Borges N, Santalo J, and Ibanez E.2010. Comparison between the Effects of Valproic Acid andTrichostatin A on the In Vitro Development, Blastocyst Quality, and Full-Term Development ofMouse Somatic Cell Nuclear Transfer Embryos. Cellular Reprogramming,12(4):437-446
Cui X S, Zhang D X, Ko Y G, and Kim N H.2009. Aberrant epigenetic reprogramming of imprintedmicroRNA-127and Rtl1in cloned mouse embryos. Biochem Biophys Res Commun,379(2):390-394
Cui X S, Xu Y N, Shen X H, Zhang L Q, Zhang J B, and Kim N H.2011. Trichostatin A modulatesapoptotic-related gene expression and improves embryo viability in cloned bovine embryos.Cellular Reprogramming,13(2):179-189
Curchoe C L, Zhang S Q, Yang L, Page R, and Tian X C.2009. Hypomethylation trends in the intergenicregion of the imprinted IGF2and H19genes in cloned cattle. Animal Reproduction Science,116(3-4):213-225
Dai X P, Hao J, Hou X J, Hai T, Fan Y, Yu Y, Jouneau A, Wang L, and Zhou Q.2010. Somatic NucleusReprogramming Is Significantly Improved by m-Carboxycinnamic Acid Bishydroxamide, aHistone Deacetylase Inhibitor. Journal of Biological Chemistry,285(40):31002-31010
Das Z C, Gupta M K, Uhm S J, and Lee H T.2010. Increasing histone acetylation of cloned embryos, butnot donor cells, by sodium butyrate improves their in vitro development in pigs. CellularReprogramming,12(1):95-104
Dawson M A, Bannister A J, G ttgens B, Foster S D, Bartke T, Green A R, and Kouzarides T.2009. JAK2phosphorylates histone H3Y41and excludes HP1&agr; from chromatin. Nature,461(7265):819-822
De Sousa P A, King T, Harkness L, Young L E, Walker S K, and Wilmut I.2001. Evaluation of gestationaldeficiencies in cloned sheep fetuses and placentae. Biology of Reproduction,65(1):23-30
Dean W, Santos F, and Reik W.(2003). Epigenetic reprogramming in early mammalian development andfollowing somatic nuclear transfer. Semin Cell Dev Biol,14(1):93-100
Dean W, Santos F, Stojkovic M, Zakhartchenko V, Walter J, Wolf E, and Reik W.2001. Conservation ofmethylation reprogramming in mammalian development: Aberrant reprogramming in clonedembryos. Proceedings of the National Academy of Sciences of the United States of America,98(24):13734-13738
Delcuve G P, Rastegar M, and Davie J R.2009. Epigenetic control. Journal of Cellular Physiology,219(2):243-250
Deshmukh R S, strup O, strup E, Vejlsted M, Niemann H, Lucas-Hahn A, Petersen B, Li J, Callesen H,and Hyttel P.2011. DNA methylation in porcine preimplantation embryos developed in vivo andproduced by in vitro fertilization, parthenogenetic activation and somatic cell nuclear transfer.Epigenetics,6(2):177-187
Ding X, Wang Y, Zhang D, Wang Y, Guo Z, and Zhang Y.2008. Increased pre-implantation developmentof cloned bovine embryos treated with5-aza-2'-deoxycytidine and trichostatin A. Theriogenology,70(4):622-630
Dong G E, Luo J, Kumar V, and Dong Z.2010. Inhibitors of histone deacetylases suppresscisplatin-induced p53activation and apoptosis in renal tubular cells. American Journal ofPhysiology-Renal Physiology,298(2):293-300
Dovey O M, Foster C T, and Cowley S M.2010. Histone deacetylase1(HDAC1), but not HDAC2,controls embryonic stem cell differentiation. Proceedings of the National Academy of Sciences,107(18):8242-8247
Easwaran H P, Schermelleh L, Leonhardt H, and Cardoso M C.2004. Replication-independent chromatinloading of Dnmt1during G2and M phases. Embo Reports,5(12):1181-1186
Eckhardt F, Lewin J, Cortese R, Rakyan V K, Attwood J, Burger M, Burton J, Cox T V, Davies R, andDown T A.2006. DNA methylation profiling of human chromosomes6,20and22. NatureGenetics,38(12):1378-1385
Eggan K, Akutsu H, Hochedlinger K, Rideout W,3rd, Yanagimachi R, and Jaenisch R.2000.X-Chromosome inactivation in cloned mouse embryos. Science,290(5496):1578-1581
Esau C, Davis S, Murray S F, Yu X X, Pandey S K, Pear M, Watts L, Booten S L, Graham M, and McKayR.2006. miR-122regulation of lipid metabolism revealed by in vivo antisense targeting. CellMetabolism,3(2):87-98
Escamilla-Del-Arenal M, da Rocha S T, and Heard E.2011. Evolutionary diversity and developmentalregulation of X-chromosome inactivation. Hum Genet,130(2):307-327
Estève P O, Chin H G, Smallwood A, Feehery G R, Gangisetty O, Karpf A R, Carey M F, and Pradhan S.2006. Direct interaction between DNMT1and G9a coordinates DNA and histone methylationduring replication. Genes&Development,20(22):3089-3103
Esteves T C, Balbach S T, Pfeiffer M J, Arauzo-Bravo M J, Klein D C, Sinn M, and Boiani M.2011.Somatic cell nuclear reprogramming of mouse oocytes endures beyond reproductive decline.Aging Cell,10(1):80-95
Ficz G, Branco M R, Seisenberger S, Santos F, Krueger F, Hore T A, Marques C J, Andrews S, and Reik W.2011. Dynamic regulation of5-hydroxymethylcytosine in mouse ES cells and duringdifferentiation. Nature,473(7347):398-402
Fish J E, Santoro M M, Morton S U, Yu S, Yeh R F, Wythe J D, Ivey K N, Bruneau B G, Stainier D Y R,and Srivastava D.2008. miR-126regulates angiogenic signaling and vascular integrity.Developmental Cell,15(2):272-284
Fouladi-Nashta A A, Gutierrez C G, Gong J G, Garnsworthy P C, and Webb R.2007. Impact of dietary fattyacids on oocyte quality and development in lactating dairy cows. Biology of Reproduction,77(1):9-17
Fu Y F, Du T T, Dong M, Zhu K Y, Jing C B, Zhang Y, Wang L, Fan H B, Chen Y, and Jin Y.2009. mir-144selectively regulates embryonic α-hemoglobin synthesis during primitive erythropoiesis. Blood,113(6):1340-1349
Fukuda A, Cao F, Morita S, Yamada K, Jincho Y, Tane S, Sotomaru Y, and Kono T.2010. Identification ofinappropriately reprogrammed genes by large-scale transcriptome analysis of individual clonedmouse blastocysts. Plos One,5(6): e11274
Galli C, Lagutina I, Crotti G, Colleoni S, Turini P, Ponderato N, Duchi R, and Lazzari G.2003. A clonedhorse born to its dam twin (vol424, pg635,2003). Nature,425(6959):680-680
Gardiner-Garden M, and Frommer M.1987. CpG islands in vertebrate genomes. Journal of MolecularBiology,196(2):261-282
Ge Y Z, Pu M T, Gowher H, Wu H P, Ding J P, Jeltsch A, and Xu G L.2004. Chromatin targeting of denovo DNA methyltransferases by the PWWP domain. Journal of Biological Chemistry,279(24):25447-25454
Gicquel C, Rossignol S, Cabrol S, Houang M, Steunou V, Barbu V, Danton F, Thibaud N, Le Merrer M,Burglen L, Bertrand A M, Netchine I, and Le Bouc Y.2005. Epimutation of the telomericimprinting center region on chromosome11p15in Silver-Russell syndrome. Nature Genetics,37(9):1003-1007
Gill G.2003. Post-translational modification by the small ubiquitin-related modifier SUMO has big effectson transcription factor activity. Current Opinion in Genetics&Development,13(2):108-113
Glazov E A, Kongsuwan K, Assavalapsakul W, Horwood P F, Mitter N, and Mahony T J.2009. Repertoireof bovine miRNA and miRNA-like small regulatory RNAs expressed upon viral infection. PlosOne,4(7): e6349
Gong G, Dai Y, Fan B, Zhu H, Wang H, Wang L, and Fang C.2004. Production of transgenic blastocystsby nuclear transfer from different types of somatic cells in cattle. Sci China Ser C,47(1):83–189
Gopichandran N, and Leese H J.2006. The effect of paracrine/autocrine interactions on the in vitro cultureof bovine preimplantation embryos. Reproduction,131(2):269-277
Gore A, Li Z, Fung H L, Young J E, Agarwal S, Antosiewicz-Bourget J, Canto I, Giorgetti A, Israel M A,Kiskinis E, Lee J H, Loh Y H, Manos P D, Montserrat N, Panopoulos A D, Ruiz S, Wilbert M L,Yu J Y, Kirkness E F, Belmonte J C I, Rossi D J, Thomson J A, Eggan K, Daley G Q, Goldstein LS B, and Zhang K.2011. Somatic coding mutations in human induced pluripotent stem cells.Nature,471(7336):63-76
Gottipati S, Rao N L, and Fung-Leung W P.2008. IRAK1: a critical signaling mediator of innate immunity.Cellular signalling,20(2):269-276
Grunder E, D'Ambrosio R, Fiaschetti G, Abela L, Arcaro A, Zuzak T, Ohgaki H, Lv S Q, Shalaby T, andGrotzer M.2011. MicroRNA-21suppression impedes medulloblastoma cell migration. EuropeanJournal of Cancer,47(16):2479-2490
Gu T P, Guo F, Yang H, Wu H P, Xu G F, Liu W, Xie Z G, Shi L, He X, Jin S G, Iqbal K, Shi Y G, Deng Z,Szabo P E, Pfeifer G P, Li J, and Xu G L.2011. The role of Tet3DNA dioxygenase in epigeneticreprogramming by oocytes. Nature,477(7366):606-610
Gu Z, Eleswarapu S, and Jiang H.2007. Identification and characterization of microRNAs from the bovineadipose tissue and mammary gland. Febs Letters,581(5):981-988
GuangXian X, Yan Z, Hao J, Juan L, XiaoMing L, Engelhardt J, and YuJiong W.2009. Cloning andidentification of microRNAs in bovine alveolar macrophages. Molecular and CellularBiochemistry,332(1/2):9-16
Hajkova P, Erhardt S, Lane N, Haaf T, El-Maarri O, Reik W, Walter J, and Surani M A.2002. Epigeneticreprogramming in mouse primordial germ cells. Mech Dev,117(1-2):15-23
Han D W, Song S J, Uhum S J, Do J T, Kim N H, Chung K S, and Lee H T.2003. Expression of IGF2andIGF receptor mRNA in bovine nuclear transferred embryos. Zygote,11(3):245-252
Han J, Lee Y, Yeom K H, Kim Y K, Jin H, and Kim V N.2004. The Drosha-DGCR8complex in primarymicroRNA processing. Genes&Development,18(24):3016-3027
Hark A T, Schoenherr C J, Katz D J, Ingram R S, Levorse J M, and Tilghman S M.2000. CTCF mediatesmethylation-sensitive enhancer-blocking activity at the H19/Igf2locus. Nature,405(6785):486-489
He Y F, Li B Z, Li Z, Liu P, Wang Y, Tang Q, Ding J, Jia Y, Chen Z, Li L, Sun Y, Li X, Dai Q, Song C X,Zhang K, He C, and Xu G L.2011. Tet-mediated formation of5-carboxylcytosine and its excisionby TDG in mammalian DNA. Science,333(6047):1303-1307
Hill J R, Edwards J F, Sawyer N, Blackwell C, and Cibelli J B.2001. Placental anomalies in a viablecloned calf. Cloning,3(2):83-88
Hill J R, Winger Q A, Long C R, Looney C R, Thompson J A, and Westhusin M E.2000. Developmentrates of male bovine nuclear transfer embryos derived from adult and fetal cells. Biology ofReproduction,62(5):1135-1140
Himaki T, Yokomine T A, Sato M, Takao S, Miyoshi K, and Yoshida M.2010. Effects of trichostatin A onin vitro development and transgene function in somatic cell nuclear transfer embryos derived fromtransgenic Clawn miniature pig cells. Animal Science Journal,81(5):558-563
Hochedlinger K, and Plath K.2009. Epigenetic reprogramming and induced pluripotency. Development,136(4):509-523
Hodawadekar S, and Marmorstein R.2007. Chemistry of acetyl transfer by histone modifying enzymes:structure, mechanism and implications for effector design. Oncogene,26(37):5528-5540
Holmgren C, Kanduri C, Dell G, Ward A, Mukhopadhya R, Kanduri M, Lobanenkov V, and Ohlsson R.2001. CpG methylation regulates the Igf2/H19insulator. Current Biology,11(14):1128-1130
Holmberg J, Armulik A, Senti K A, Edoff K, Spalding K, Momma S, Cassidy R, Flanagan J G, and Frisén J.2005. Ephrin-A2reverse signaling negatively regulates neural progenitor proliferation andneurogenesis. Genes&Development,19(4):462-471
Hong Y, Yang J, Chi Y, Wang W, Wu W, Yun X, Kong X, and Gu J.2010. BCL2L12A localizes to the cellnucleus and induces growth inhibition through G2/M arrest in CHO cells. Molecular and CellularBiochemistry,333(1):323-330
Hu S, Xie Z, Onishi A, Yu X, Jiang L, Lin J, Rho H, and Woodard C.2009. Profiling the humanprotein-DNA interactome reveals ERK2as a transcriptional repressor of interferon signaling. Cell,139(3):610-622
Humpherys D, Eggan K, Akutsu H, Friedman A, Hochedlinger K, Yanagimachi R, Lander E S, Golub T R,and Jaenisch R.2002. Abnormal gene expression in cloned mice derived from embryonic stemcell and cumulus cell nuclei. Proc Natl Acad Sci U S A,99(20):12889-12894
Humpherys D, Eggan K, Akutsu H, Hochedlinger K, Rideout W M, Biniszkiewicz D, Yanagimachi R, andJaenisch R.2001. Epigenetic instability in ES cells and cloned mice. Science,293(5527):95-97
Hurst D R, Edmonds M D, Scott G K, Benz C C, Vaidya K S, and Welch D R.2009. Breast cancermetastasis suppressor1up-regulates miR-146, which suppresses breast cancer metastasis. CancerResearch,69(4):1279-1283
Hussein S M, Batada N N, Vuoristo S, Ching R W, Autio R, Narva E, Ng S, Sourour M, Hamalainen R,Olsson C, Lundin K, Mikkola M, Trokovic R, Peitz M, Brustle O, Bazett-Jones D P, Alitalo K,Lahesmaa R, Nagy A, and Otonkoski T.2011. Copy number variation and selection duringreprogramming to pluripotency. Nature,471(7336):58-62
Hwang J H, Voortman J, Giovannetti E, Steinberg S M, Leon L G, Kim Y T, Funel N, Park J K, Kim M A,Kang G H, Kim S W, Del Chiaro M, Peters G J, and Giaccone G.2010. Identification ofmicroRNA-21as a biomarker for chemoresistance and clinical outcome following adjuvanttherapy in resectable pancreatic cancer. Plos One,5(5): e10630
Hyun S H, Lee G S, Kim D Y, Kim H S, Lee S H, Kim S, Lee E S, Lim J M, Kang S K, Lee B C, andHwang W S.2003. Effect of maturation media and oocytes derived from sows or gilts on thedevelopment of cloned pig embryos. Theriogenology,59(7):1641-1649
Iager A E, Ragina N P, Ross P J, Beyhan Z, Cunniff K, Rodriguez R M, and Cibelli J B.2008. Trichostatina improves histone acetylation in bovine somatic cell nuclear transfer early embryos. Cloning andStem Cells,10(3):371-379
Ideraabdullah F Y, Vigneau S, and Bartolomei M S.2008. Genomic imprinting mechanisms in mammals.Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis,647(1-2):77-85
Inoue A, Shen L, Dai Q, He C, and Zhang Y.2011. Generation and replication-dependent dilution of5fCand5caC during mouse preimplantation development. Cell Research,21(12):1670-1676
Inoue A, and Zhang Y.2011. Replication-dependent loss of5-hydroxymethylcytosine in mousepreimplantation embryos. Science,334(6053):194
Inoue K, Kohda T, Lee J, Ogonuki N, Mochida K, Noguchi Y, Tanemura K, Kaneko-Ishino T, Ishino F, andOgura A.2002. Faithful expression of imprinted genes in cloned mice. Science,295(5553):297-297
Inoue K, Kohda T, Sugimoto M, Sado T, Ogonuki N, Matoba S, Shiura H, Ikeda R, Mochida K, Fujii T,Sawai K, Otte A P, Tian X C, Yang X, Ishino F, Abe K, and Ogura A.2010. Impeding Xistexpression from the active X chromosome improves mouse somatic cell nuclear transfer. Science,330(6003):496-499
Iqbal K, Jin S G, Pfeifer G P, and Szabo P E.2011. Reprogramming of the paternal genome uponfertilization involves genome-wide oxidation of5-methylcytosine. Proc Natl Acad Sci U S A,108(9):3642-3647
Irie N, Takada Y, Watanabe Y, Matsuzaki Y, Naruse C, Asano M, Iwakura Y, Suda T, and Matsuo K.2009.Bidirectional signaling through ephrinA2-EphA2enhances osteoclastogenesis and suppressesosteoblastogenesis. Journal of Biological Chemistry,284(21):14637-14644
Ito S, D'Alessio A C, Taranova O V, Hong K, Sowers L C, and Zhang Y.2010. Role of Tet proteins in5mCto5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature,466(7310):1129-1133
Ito S, Shen L, Dai Q, Wu S C, Collins L B, Swenberg J A, He C, and Zhang Y.2011. Tet Proteins CanConvert5-Methylcytosine to5-Formylcytosine and5-Carboxylcytosine. Science,333(6047):1300-1303
Jin W, Dodson M V, Moore S S, Basarab J A, and Guan L L.2010. Characterization of microRNAexpression in bovine adipose tissues: a potential regulatory mechanism of subcutaneous adiposetissue development. Bmc Molecular Biology,11(1):29
Jinno Y, Sengoku K, Nakao M, Tamate K, Miyamoto T, Matsuzaka T, Sutcliffe JS, Anan T, Takuma N, andNishiwaki K I Y, Ishimaru T, Ishikawa M, Niikawa N.1996. Mouse/human sequence divergencein a region with a paternal-specific methylation imprint at the human H19locus. Hum Mol Genet,5(8):1155-1161
Jones P L, Veenstra G J C, Wade P A, Vermaak D, Kass S U, Landsberger N, Strouboulis J, and Wolffe A P.1998. Methylated DNA and MeCP2recruit histone deacetylase to repress transcription. NatureGenetics,19(2):187-191
Joyce J A, Lam W K, Catchpoole D J, Jenks P, Reik W, Maher E R, and Schofield P N.1997. Imprinting ofIGF2and H19: Lack of reciprocity in sporadic Beckwith-Wiedemann syndrome. HumanMolecular Genetics,6(9):1543-1548
Jurkowski T P, Meusburger M, Phalke S, Helm M, Nellen W, Reuter G, and Jeltsch A.2008. HumanDNMT2methylates tRNA(Asp) molecules using a DNA methyltransferase-like catalyticmechanism. Rna-a Publication of the Rna Society,14(8):1663-1670
Kalantry S, Purushothaman S, Bowen R B, Starmer J, and Magnuson T.2009. Evidence of XistRNA-independent initiation of mouse imprinted X-chromosome inactivation. Nature,460(7255):647-651
Kanduri C, Pant V, Loukinov D, Pugacheva E, Qi C F, Wolffe A, Ohlsson R, and Lobanenkov V V.2000.Functional association of CTCF with the insulator upstream of the H19gene is parent oforigin-specific and methylation-sensitive. Current Biology,10(14):853-856
Kaneda A, and Feinberg A P.2005. Loss of imprinting of IGF2: a common epigenetic modifier of intestinaltumor risk. Cancer Research,65(24):11236-11240
Kanehisa M, Araki M, Goto S, Hattori M, Hirakawa M, Itoh M, Katayama T, Kawashima S, Okuda S,Tokimatsu T, and Yamanishi Y.2008. KEGG for linking genomes to life and the environment.Nucleic Acids Research,36(Database issue): D480-D484
Kang Y K, Koo D B, Park J S, Choi Y H, Chung A S, Lee K K, and Han Y M.2001. Aberrant methylationof donor genome in cloned bovine embryos. Nature Genetics,28(2):173-177
Kano M, Seki N, Kikkawa N, Fujimura L, Hoshino I, Akutsu Y, Chiyomaru T, Enokida H, Nakagawa M,and Matsubara H.2010. miR‐145, miR‐133a and miR‐133b: Tumor‐suppressive miRNAstarget FSCN1in esophageal squamous cell carcinoma. International Journal of Cancer,127(12):2804-2814
Kato Y, Tani T, Sotomaru Y, Kurokawa K, Kato J, Doguchi H, Yasue H, and Tsunoda Y.1998. Eight calvescloned from somatic cells of a single adult. Science,282(5396):2095-2098
Kato Y, Tani T, and Tsunoda Y.2000. Cloning of calves from various somatic cell types of male and femaleadult, newborn and fetal cows. Journal of Reproduction and Fertility,120(2):231-237
Katz-Jaffe M G, McCallie B R, Preis K A, Filipovits J, and Gardner D K.2009. Transcriptome analysis ofin vivo and in vitro matured bovine MII oocytes. Theriogenology,71(6):939-946
Kishigami S, Mizutani E, Ohta H, Hikichi T, Van Thuan N, Wakayama S, Bui H T, and Wakayama T.2006.Significant improvement of mouse cloning technique by treatment with trichostatin A aftersomatic nuclear transfer. Biochemical and Biophysical Research Communications,340(1):183-189
Koh K P, Yabuuchi A, Rao S, Huang Y, Cunniff K, Nardone J, Laiho A, Tahiliani M, Sommer C A,Mostoslavsky G, Lahesmaa R, Orkin S H, Rodig S J, Daley G Q, and Rao A.2011. Tet1and Tet2regulate5-hydroxymethylcytosine production and cell lineage specification in mouse embryonicstem cells. Cell Stem Cell,8(2):200-213
Krek A, Grun D, Poy M N, Wolf R, Rosenberg L, Epstein E J, MacMenamin P, da Piedade I, Gunsalus K C,Stoffel M, and Rajewsky N.2005. Combinatorial microRNA target predictions. Nature Genetics,37(5):495-500
Kubota C, Tian X C, and Yang X Z.2004. Serial bull cloning by somatic cell nuclear transfer. NatureBiotechnology,22(6):693-694
Kubota C, Yamakuchi H, Todoroki J, Mizoshita K, Tabara N, Barber M, and Yang X Z.2000. Six clonedcalves produced from adult fibroblast cells after long-term culture. Proceedings of the NationalAcademy of Sciences of the United States of America,97(3):990-995
Lan F, and Shi Y.2009. Epigenetic regulation: methylation of histone and non-histone proteins. Science inChina Series C: Life Sciences,52(4):311-322
Lan J, Hua S, He X N, and Zhang Y.2010. DNA methyltransferases and methyl-binding proteins ofmammals. Acta Biochimica Et Biophysica Sinica,42(4):243-252
Lee B C, Kim M K, Jang G, Oh H J, Yuda F, Kim H J, Shamim M H, Kim J J, Kang S K, Schatten G, andHwang W S.2005. Dogs cloned from adult somatic cells. Nature,436(7051):641-641
Lee D Y, Hayes J J, Pruss D, and Wolffe A P.1993a. A Positive Role for Histone Acetylation inTranscription Factor Access to Nucleosomal DNA. Cell,72(1):73-84
Lee E, Estrada J, and Piedrahita J A.2008. A comparative study on the efficiency of two enucleationmethods in pig somatic cell nuclear transfer: Effects of the squeezing and the aspiration methods.Animal Biotechnology,19(2):71-79
Lee J H, and Campbell K H S.2006. Effects of enucleation and caffeine on maturation-promoting factor(MPF) and mitogen-activated protein kinase (MAPK) activities in ovine oocytes used as recipientcytoplasts for nuclear transfer. Biology of Reproduction,74(4):691-698
Lee R C, Feinbaum R L, and Ambros V.1993b. The C. elegans heterochronic gene lin-4encodes smallRNAs with antisense complementarity to lin-14. Cell,75(5):843-854
Lehnertz B, Ueda Y, Derijck A A H A, Braunschweig U, Perez-Burgos L, Kubicek S, Chen T, Li E,Jenuwein T, and Peters A H F M.2003. Suv39h-Mediated Histone H3Lysine9MethylationDirects DNA Methylation to Major Satellite Repeats at Pericentric Heterochromatin. CurrentBiology,13(14):1192-1200
Lewis B P, Burge C B, and Bartel D P.2005. Conserved seed pairing, often flanked by adenosines,indicates that thousands of human genes are microRNA targets. Cell,120(1):15-20
Li E.2002. Chromatin modification and epigenetic reprogramming in mammalian development. NatureReviews Genetics,3(9):662-673
Li E, Beard C, and Jaenisch R.1993. Role for DNA Methylation in Genomic Imprinting. Nature,366(6453):362-365
Li J, Svarcova O, Villemoes K, Kragh P M, Schmidt M, Bogh I B, Zhang Y, Du Y, Lin L, Purup S, Xue Q,Bolund L, Yang H, Maddox-Hyttel P, and Vajta G.2008a. High in vitro development after somaticcell nuclear transfer and trichostatin A treatment of reconstructed porcine embryos.Theriogenology,70(5):800-808
Li L C, and Dahiya R.2002. MethPrimer: designing primers for methylation PCRs. Bioinformatics,18(11):1427-1431
Li N, Ye M, Li Y, Yan Z, Butcher L M, Sun J, Han X, Chen Q, Zhang X, and Wang J.2010. Whole genomeDNA methylation analysis based on high throughput sequencing technology. Methods,52(3):203-212
Li Q, Li N, Hu X, Li J, Du Z, Chen L, Yin G, Duan J, Zhang H, and Zhao Y.2011. Genome-wide mappingof DNA methylation in chicken. Plos One,6(5): e19428
Li R, Yu C, Li Y, Lam T W, Yiu S M, Kristiansen K, and Wang J.2009a. SOAP2: an improved ultrafasttool for short read alignment. Bioinformatics,25(15):1966-1967
Li S J, Li Y X, Du W H, Zhang L, Yu S Y, Dai Y P, Zhao C J, and Li N.2005. Aberrant gene expression inorgans of bovine clones that die within two days after birth. Biology of Reproduction,72(2):258-265
Li X, Wang X, He K, Ma Y, Su N, He H, Stolc V, Tongprasit W, Jin W, and Jiang J.2008b. High-resolutionmapping of epigenetic modifications of the rice genome uncovers interplay between DNAmethylation, histone methylation, and gene expression. The Plant Cell Online,20(2):259-276
Li X, Yan P, and Shao Z.2009b. Downregulation of miR-193b contributes to enhance urokinase-typeplasminogen activator (uPA) expression and tumor progression and invasion in human breastcancer. Oncogene,28(44):3937-3948
Li Y, and Sasaki H.2011. Genomic imprinting in mammals: its life cycle, molecular mechanisms andreprogramming. Cell Research,21(3):466-473
Li Z Y, Sun X S, Chen J, Liu X M, Wisely S M, Zhou Q, Renard J P, Leno G H, and Engelhardt J F.2006.Cloned ferrets produced by somatic cell nuclear transfer. Developmental Biology,293(2):439-448
Lim L P, Lau N C, Garrett-Engele P, Grimson A, Schelter J M, Castle J, Bartel D P, Linsley P S, andJohnson J M.2005. Microarray analysis shows that some microRNAs downregulate largenumbers of target mRNAs. Nature,433(7027):769-773
Lin L, Li Q, Zhang L, Zhao D S, Dai Y P, and Li N.2008. Aberrant epigenetic changes and geneexpression in cloned cattle dying around birth. Bmc Developmental Biology,8(14):1-10
Lister R, Pelizzola M, Dowen R H, Hawkins R D, Hon G, Tonti-Filippini J, Nery J R, Lee L, Ye Z, Ngo QM, Edsall L, Antosiewicz-Bourget J, Stewart R, Ruotti V, Millar A H, Thomson J A, Ren B, andEcker J R.2009. Human DNA methylomes at base resolution show widespread epigenomicdifferences. Nature,462(7271):315-322
Lister R, Pelizzola M, Kida Y S, Hawkins R D, Nery J R, Hon G, Antosiewicz-Bourget J, O'Malley R,Castanon R, Klugman S, Downes M, Yu R, Stewart R, Ren B, Thomson J A, Evans R M, andEcker J R.2011. Hotspots of aberrant epigenomic reprogramming in human induced pluripotentstem cells. Nature,471(7336):68-84
Liu F J, Zhang Y, Zheng Y M, Zhao M T, Zhang Y L, Wang Y S, Wang G H, Quan F S, and An Z X.2007.Optimization of electrofusion protocols for somatic cell nuclear transfer. Small Ruminant Research,73(1-3):246-251
Liu J H, Yin S, Xiong B, Hou Y, Chen D Y, and Sun Q Y.2008. Aberrant DNA methylation imprints inaborted bovine clones. Molecular Reproduction and Development,75(4):598-607
Liu N, Enkemann S A, Liang P, Hersmus R, Zanazzi C, Huang J, Wu C, Chen Z, Looijenga L H J, andKeefe D L.2010. Genome-wide gene expression profiling reveals aberrant MAPK and Wntsignaling pathways associated with early parthenogenesis. Journal of molecular cell biology,2(6):333-344
Loenarz C, and Schofield C J.2011. Physiological and biochemical aspects of hydroxylations anddemethylations catalyzed by human2-oxoglutarate oxygenases. Trends in Biochemical Sciences,36(1):7-18
Loi P, Ledda S, Fulka J, Jr., Cappai P, and Moor R M.1998. Development of parthenogenetic and clonedovine embryos: effect of activation protocols. Biology of Reproduction,58(5):1177-1187
Lonergan P, Monaghan P, Rizos D, Boland M P, and Gordon I.1994. Effect of follicle size on bovineoocyte quality and developmental competence following maturation, fertilization, and culture invitro. Molecular Reproduction and Development,37(1):48-53
Long J E, and Cai X.2007. Igf-2r expression regulated by epigenetic modification and the locus of geneimprinting disrupted in cloned cattle. Gene,388(1-2):125-134
Long J E, Cai X, and He L Q.2007. Gene profiling of cattle blastocysts derived from nuclear transfer, invitro fertilization and in vivo development based on cDNA library. Animal Reproduction Science,100(3-4):243-256
Lorsbach R, Moore J, Mathew S, Raimondi S, Mukatira S, and Downing J.2003. TET1, a member of anovel protein family, is fused to MLL in acute myeloid leukemia containing the t(10;11)(q22;q23). Leukemia,17(3):637-641
Lucifero D, Mertineit C, Clarke H J, Bestor T H, and Trasler J M.2002. Methylation dynamics ofimprinted genes in mouse germ cells. Genomics,79(4):530-538
Lucifero D, Suzuki J, Bordignon V, Martel J, Vigneault C, Therrien J, Filion F, Smith L C, and Trasler J M.2006. Bovine SNRPN methylation imprint in oocytes and day17in vitro-produced and somaticcell nuclear transfer embryos. Biology of Reproduction,75(4):531-538
Ma L, Reinhardt F, Pan E, Soutschek J, Bhat B, Marcusson E G, Teruya-Feldstein J, Bell G W, andWeinberg R A.2010. Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammarytumor model. Nature Biotechnology,28(4):341-347
Ma L, Teruya-Feldstein J, and Weinberg R A.2007. Tumour invasion and metastasis initiated bymicroRNA-10b in breast cancer. Nature,449(7163):682-688
Ma S F, Liu X Y, Miao D Q, Han Z B, Zhang X, Miao Y L, Yanagimachi R, and Tan J H.2005.Parthenogenetic activation of mouse oocytes by strontium chloride: a search for the bestconditions. Theriogenology,64(5):1142-1157
Maalouf W E, Liu Z C, Brochard V, Renard J P, Debey P, Beaujean N, and Zink D.2009. Trichostatin Atreatment of cloned mouse embryos improves constitutive heterochromatin remodeling as well asdevelopmental potential to term. Bmc Developmental Biology,9(11):1-6
Maatouk D M, and Resnick J L.2003. Continuing primordial germ cell differentiation in the mouseembryo is a cell-intrinsic program sensitive to DNA methylation. Developmental Biology,258(1):201-208
Maiti A, and Drohat A C.2011. Thymine DNA glycosylase can rapidly excise5-formylcytosine and5-carboxylcytosine: Potential implications for active demethylation of CpG sites. Journal ofBiological Chemistry,286(41):35334-3538
Mallory A C, and Vaucheret H.2006. Functions of microRNAs and related small RNAs in plants. NatureGenetics,38Suppl: S31-S36
Mann M R W, Chung Y G, Nolen L D, Verona R I, Latham K E, and Bartolomei M S.2003. Disruption ofimprinted gene methylation and expression in cloned preimplantation stage mouse embryos.Biology of Reproduction,69(3):902-914
Masui S, Nakatake Y, Toyooka Y, Shimosato D, Yagi R, Takahashi K, Okochi H, Okuda A, Matoba R,Sharov A A, Ko M S H, and Niwa H.2007. Pluripotency governed by Sox2via regulation ofOct3/4expression in mouse embryonic stem cells. Nature Cell Biology,9(6):625-626
Matoba S, Inoue K, Kohda T, Sugimoto M, Mizutani E, Ogonuki N, Nakamura T, Abe K, Nakano T, IshinoF, and Ogura A.2011. RNAi-mediated knockdown of Xist can rescue the impairedpostimplantation development of cloned mouse embryos. Proc Natl Acad Sci U S A,108(51):20621-20626
Md H, Nasser G, Michael H, Franca R, Chirawath P, Ernst T, Karl S, and Dawit T.2009. Identification andcharacterization of miRNAs expressed in the bovine ovary. Bmc Genomics,10:443
Meissner A, Mikkelsen T S, Gu H, Wernig M, Hanna J, Sivachenko A, Zhang X, Bernstein B E, NusbaumC, and Jaffe D B.2008. Genome-scale DNA methylation maps of pluripotent and differentiatedcells. Nature,454(7205):766-770
Meng F, Henson R, Lang M, Wehbe H, Maheshwari S, Mendell J T, Jiang J, Schmittgen T D, and Patel T.2006. Involvement of human micro-RNA in growth and response to chemotherapy in humancholangiocarcinoma cell lines. Gastroenterology,130(7):2113-2129
Meng Q G, Polgar Z, Liu J, and Dinnyes A.2009. Live Birth of Somatic Cell-Cloned Rabbits followingTrichostatin A Treatment and Cotransfer of Parthenogenetic Embryos. Cloning and Stem Cells,11(1):203-208
Mendez M G, Kojima S I, and Goldman R D.2010. Vimentin induces changes in cell shape, motility, andadhesion during the epithelial to mesenchymal transition. The FASEB Journal,24(6):1838-1851
Miglino M A, Pereira F T V, Visintin J A, Garcia J M, Meirelles F V, Rumpf R, Ambrosio C E, Papa P C,Santos T C, Carvalho A F, Leiser R, and Carter A M.2007. Placentation in cloned cattle: Structureand microvascular architecture. Theriogenology,68(4):604-617
Mikkelsen T S, Ku M, Jaffe D B, Issac B, Lieberman E, Giannoukos G, Alvarez P, Brockman W, Kim T K,and Koche R P.2007. Genome-wide maps of chromatin state in pluripotent and lineage-committedcells. Nature,448(7153):553-560
Miles J R, McDaneld T G, Wiedmann R T, Cushman R A, Echternkamp S E, Vallet J L, and Smith T P.2012. MicroRNA expression profile in bovine cumulus-oocyte complexes: possible role of let-7and miR-106a in the development of bovine oocytes. Animal Reproduction Science,130(1-2):16-26
Misri S, Pandita S, Kumar R, and Pandita T.2008. Telomeres, histone code, and DNA damage response.Cytogenetic and Genome Research,122(3-4):297-307
Miyoshi K, Mori H, Mizobe Y, Akasaka E, Ozawa A, Yoshida M, and Sato M.2010. Valproic acidenhances in vitro development and Oct-3/4expression of miniature pig somatic cell nucleartransfer embryos. Cellular Reprogramming,12(1):67-74
Miyoshi K, Rzucidlo S J, Pratt S L, and Stice S L.2003. Improvements in cloning efficiencies may bepossible by increasing uniformity in recipient oocytes and donor cells. Biology of Reproduction,68(4):1079-1086
Mortazavi A, Williams B A, McCue K, Schaeffer L, and Wold B.2008. Mapping and quantifyingmammalian transcriptomes by RNA-Seq. Nature Methods,5(7):621-628
Murrell A, Heeson S, and Reik W.2004. Interaction between differentially methylated regions partitionsthe imprinted genes Igf2and H19into parent-specific chromatin loops. Nature Genetics,36(8):889-893
Nagayoshi S, Hayashi E, Abe G, Osato N, Asakawa K, Urasaki A, Horikawa K, Ikeo K, Takeda H, andKawakami K.2008. Insertional mutagenesis by the Tol2transposon-mediated enhancer trapapproach generated mutations in two developmental genes: tcf7and synembryn-like. Development,135(1):159-169
Nahid M A, Pauley K M, Satoh M, and Chan E K L.2009. miR-146a Is Critical for Endotoxin-inducedTolerance. Journal of Biological Chemistry,284(50):34590-34599
Nan X, Ng H H, Johnson C A, Laherty C D, Turner B M, Eisenman R N, and Bird A.1998. Transcriptionalrepression by the methyl-CpG-binding protein MeCP2involves a histone deacetylase complex.Nature,393(6683):386-389
Niwa H, Toyooka Y, Shimosato D, Strumpf D, Takahashi K, Yagi R, and Rossant J.2005. Interactionbetween Oct3/4and Cdx2determines trophectoderm differentiation. Cell,123(5):917-930
Ng S, Yue W, Oppermann U, and Klose R.2009. Dynamic protein methylation in chromatin biology.Cellular and Molecular Life Sciences,66(3):407-422
Noble J A, White A M, Lazzeroni L C, Valdes A M, Mirel D B, Reynolds R, Grupe A, Aud D, Peltz G, andErlich H A.2003. A polymorphism in the TCF7gene, C883A, is associated with type1diabetes.Diabetes,52(6):1579-1582
Noonan E.2009. miR-449a targets HDAC-1and induces growth arrest in prostate cancer. Oncogene,28(14):1714-1724
Noonan E J.2010. miR-449a causes Rb-dependent cell cycle arrest and senescence in prostate cancer cells.Oncotarget,1(5):349-358
Norris D P, Patel D, Kay G F, Penny G D, Brockdorff N, Sheardown S A, and Rastan S.1994. Evidencethat random and imprinted Xist expression is controlled by preemptive methylation. Cell,77(1):41-51
Nowak S J, and Corces V G.2004. Phosphorylation of histone H3: a balancing act between chromosomecondensation and transcriptional activation. Trends in Genetics,20(4):214-220
Oback B, and Wells D N.2003. Cloning cattle. Cloning and Stem Cells,5(4):243-256
Ogawa H, Ono Y, Shimozawa N, Sotomaru Y, Katsuzawa Y, Hiura H, Ito M, and Kono T.2003. Disruptionof imprinting in cloned mouse fetuses from embryonic stem cells. Reproduction,126(4):549-557
Ogonuki N, Inoue K, Yamamoto Y, Noguchi Y, Tanemura K, Suzuki O, Nakayama H, Doi K, Ohtomo Y,Satoh M, Nishida A, and Ogura A.2002. Early death of mice cloned from somatic cells. NatureGenetics,30(3):253-254
Ogura A, Inoue K, Ogonuki N, Noguchi A, Takano K, Nagano R, Suzuki O, Lee J, Ishino F, and Matsuda J.2000. Production of male cloned mice from fresh, cultured, and cryopreserved immature Sertolicells. Biology of Reproduction,62(6):1579-1584
Okamoto I, Patrat C, Thepot D, Peynot N, Fauque P, Daniel N, Diabangouaya P, Wolf J P, Renard J P,Duranthon V, and Heard E.2011. Eutherian mammals use diverse strategies to initiateX-chromosome inactivation during development. Nature,472(7343):370-374
Oki M, Aihara H, and Ito T.2007. Role of histone phosphorylation in chromatin dynamics and itsimplications in diseases. Chromatin and Disease,41:323-340
Onishi A, Iwamoto M, Akita T, Mikawa S, Takeda K, Awata T, Hanada H, and Perry A C F.2000. Pigcloning by microinjection of fetal fibroblast nuclei. Science,289(5482):1188-1190
Ono R, Taki T, Taketani T, Taniwaki M, Kobayashi H, and Hayashi Y.2002. LCX, leukemia-associatedprotein with a CXXC domain, is fused to MLL in acute myeloid leukemia with trilineagedysplasia having t(10;11)(q22;q23). Cancer Research,62(14):4075-4080
Ono T, Li C, Mizutani E, Terashita Y, Yamagata K, and Wakayama T.2010. Inhibition of Class IIb HistoneDeacetylase Significantly Improves Cloning Efficiency in Mice. Biology of Reproduction,83(6):929-937
Pérez-Cadahía B P C B, Drobic B D B, and Davie J R D J R.2009. H3phosphorylation: dual role inmitosis and interphase This paper is one of a selection of papers published in this Special Issueentitled30th Annual International Asilomar Chromatin and Chromosomes Conference and hasundergone the Journal's usual peer review process. Biochemistry and Cell Biology,87(5):695-709
Park J Y, Park M R, Hwang K C, Chung J S, Bui H T, Kim T, Cho S K, Kim J H, Hwang S, Park S B, andNguyen V T.2011. Comparative gene expression analysis of somatic cell nuclear transfer-derivedcloned pigs with normal and abnormal umbilical cords. Biology of Reproduction,84(1):189-99
Parthun M.2007. Hat1: the emerging cellular roles of a type B histone acetyltransferase. Oncogene,26(37):5319-5328
Pase L, Layton J E, Kloosterman W P, Carradice D, Waterhouse P M, and Lieschke G J.2009. miR-451regulates zebrafish erythroid maturation in vivo via its target gata2. Blood,113(8):1794-1804
Pastor W A, Pape U J, Huang Y, Henderson H R, Lister R, Ko M, McLoughlin E M, Brudno Y, MahapatraS, Kapranov P, Tahiliani M, Daley G Q, Liu X S, Ecker J R, Milos P M, Agarwal S, and Rao A.2011. Genome-wide mapping of5-hydroxymethylcytosine in embryonic stem cells. Nature,473(7347):394-397
Penn N, Suwalski R, O'Riley C, Bojanowski K, and Yura R.1972. The presence of5-hydroxymethylcytosine in animal deoxyribonucleic acid. Biochemical Journal,126(4):781-790
Pfaffeneder T, Hackner B, Tru M, Münzel M, Müller M, Deiml C A, Hagemeier C, and Carell T.2011.The Discovery of5‐Formylcytosine in Embryonic Stem Cell DNA.Angewandte Chemie,123(31):7146-7150
Pinter S F, Sadreyev R I, Yildirim E, Jeon Y, Ohsumi T K, Borowsky M, and Lee J T.2012. Spreading of Xchromosome inactivation via a hierarchy of defined Polycomb stations. Genome Res,22(10):1864-1876
Plath K.2003. Role of histone H3lysine27methylation in X inactivation. Science,300(5616):131-135
Pokholok D K, Harbison C T, Levine S, Cole M, Hannett N M, Lee T I, Bell G W, Walker K, Rolfe P A,and Herbolsheimer E.2005. Genome-wide map of nucleosome acetylation and methylation inyeast. Cell,122(4):517-527
Popp C, Dean W, Feng S, Cokus S J, Andrews S, Pellegrini M, Jacobsen S E, and Reik W.2010.Genome-wide erasure of DNA methylation in mouse primordial germ cells is affected by AIDdeficiency. Nature,463(7284):1101-1105
Powell A M, Talbot N C, Wells K D, Kerr D E, Pursel V G, and Wall R J.2004. Cell donor influencessuccess of producing cattle by somatic cell nuclear transfer. Biology of Reproduction,71(1):210-216
Pujol M, Lopez-Bejar M, and Paramio M T.2004. Developmental competence of heifer oocytes selectedusing the brilliant cresyl blue (BCB) test. Theriogenology,61(4):735-744
Reik W, Bowden L, Constancia M, Dean W, Feil R, Forne T, Kelsey G, Maher E, Moore T, Sun F L, andWalter J.1996. Regulation of Igf2imprinting in development and disease. International Journalof Developmental Biology, Suppl1:53S-54S
Reik W, Brown K W, Schneid H, Le Bouc Y, Bickmore W, and Maher E R.1995. Imprinting mutations inthe Beckwith—Wiedemann syndrome suggested by an altered imprinting pattern in the IGF2–H19domain. Human Molecular Genetics,4(12):2379-2385
Renard J P, Chastant S, Chesne P, Richard C, Marchal J, Cordonnier N, Chavatte P, and Vignon X.1999.Lymphoid hypoplasia and somatic cloning. Lancet,353(9163):1489-1491
Rizos D, Burke L, Duffy P, Wade M, Mee J F, O'Farrell K J, Macsiurtain M, Boland M P, and Lonergan P.2005. Comparisons between nulliparous heifers and cows as oocyte donors for embryo productionin vitro. Theriogenology,63(3):939-949
Roca J, Martinez E, Vazquez J M, and Lucas X.1998. Selection of immature pig oocytes for homologousin vitro penetration assays with the brilliant cresyl blue test. Reprod Fertil Dev,10(6):479-485
Rodrigues B A, Rodriguez P, Silva A E, Cavalcante L F, Feltrin C, and Rodrigues J L.2009. Preliminarystudy in immature canine oocytes stained with brilliant cresyl blue and obtained from bitches withlow and high progesterone serum profiles. Reproduction in Domestic Animals,44Suppl2:255-258
Rodriguez-Gonzalez E, Lopez-Bejar M, Izquierdo D, and Paramio M T.2003. Developmental competenceof prepubertal goat oocytes selected with brilliant cresyl blue and matured with cysteaminesupplementation. Reproduction Nutrition Development,43(2):179-187
Rodriguez-Gonzalez E, Lopez-Bejar M, Velilla E, and Paramio M T.2002. Selection of prepubertal goatoocytes using the brilliant cresyl blue test. Theriogenology,57(5):1397-409
Ruike Y, Imanaka Y, Sato F, Shimizu K, and Tsujimoto G.2010. Genome-wide analysis of aberrantmethylation in human breast cancer cells using methyl-DNA immunoprecipitation combined withhigh-throughput sequencing. Bmc Genomics,11:137
Rybouchkin A, Kato Y, and Tsunodaz Y.2006. Role of histone acetylation in reprogramming of somaticnuclei following nuclear transfer. Biology of Reproduction,74(6):1083-1089
Sado T, and Brockdorff N.2013. Advances in understanding chromosome silencing by the longnon-coding RNA Xist. Philos Trans R Soc Lond B Biol Sci,368(1609):20110325
Sartori R, Sartor-Bergfelt R, Mertens S A, Guenther J N, Parrish J J, and Wiltbank M C.2002. Fertilizationand early embryonic development in heifers and lactating cows in summer and lactating and drycows in winter. Journal of Dairy Science,85(11):2803-2812
Sato N, Meijer L, Skaltsounis L, Greengard P, and Brivanlou A H.2004. Maintenance of pluripotency inhuman and mouse embryonic stem cells through activation of Wnt signaling by a pharmacologicalGSK-3-specific inhibitor. Nature Medicine,10(1):55-63
Schaar C, Kluin-Nelemans H, Te Marvelde C, Le Cessie S, Breed W, Fibbe W, Van Deijk W, Fickers M,Roozendaal K, and Wijermans P.2005. Interferon-α as maintenance therapy in patients withmultiple myeloma. Annals of Oncology,16(4):634-639
Shao G B, Ding H M, and Gong A H.2008a. Role of histone methylation in zygotic genome activation inthe preimplantation mouse embryo. In Vitro Cell Dev Biol Anim,44(3-4):115-120
Shao G B, Ding H M, Gong A H, and Xiao D S.2008b. Inheritance of histone H3methylation inreprogramming of somatic nuclei following nuclear transfer. J Reprod Dev,54(3):233-238
Sharif J, Muto M, Takebayashi S, Suetake I, Iwamatsu A, Endo T A, Shinga J, Mizutani-Koseki Y, ToyodaT, Okamura K, Tajima S, Mitsuya K, Okano M, and Koseki H.2007. The SRA protein Np95mediates epigenetic inheritance by recruiting Dnmt1to methylated DNA. Nature,450(7171):908-912
Shen C J, Cheng W T K, Wu S C, Chen H L, Tsai T C, Yang S H, and Chen C M.2012. DifferentialDifferences in Methylation Status of Putative Imprinted Genes among Cloned Swine Genomes.Plos One,7(2): e32812
Shen L, Kondo Y, Guo Y, Zhang J, Zhang L, Ahmed S, Shu J, Chen X, Waterland R A, and Issa J P J.2007.Genome-wide profiling of DNA methylation reveals a class of normally methylated CpG islandpromoters. Plos Genetics,3(10): e181
Shi L H, Miao Y L, Ouyang Y C, Huang J C, Lei Z L, Yang J W, Han Z M, Song X F, Sun Q Y, and ChenD Y.2008. Trichostatin a (TSA) improves the development of rabbit-rabbit intraspecies clonedembryos, but not rabbit-human interspecies cloned embryos. Developmental Dynamics,237(3):640-648
Shi W, Hoeflich A, Flaswinkel H, Stojkovic M, Wolf E, and Zakhartchenko V.2003. Induction of asenescent-like phenotype does not confer the ability of bovine immortal cells to support thedevelopment of nuclear transfer embryos. Biology of Reproduction,69(1):301-309
Shin T, Kraemer D, Pryor J, Liu L, Rugila J, Howe L, Buck S, Murphy K, Lyons L, and Westhusin M.2002. A cat cloned by nuclear transplantation. Nature,415(6874):859-859
Sibley C P, Coan P M, Ferguson-Smith A C, Dean W, Hughes J, Smith P, Reik W, Burton G J, Fowden A L,and Constancia M.2004. Placental-specific insulin-like growth factor2(Igf2) regulates thediffusional exchange characteristics of the mouse placenta. Proceedings of the National Academyof Sciences of the United States of America,101(21):8204-8208
Sleutels F, Zwart R, and Barlow D P.2002. The non-coding Air RNA is required for silencing autosomalimprinted genes. Nature,415(6873):810-813
Smallwood A, Estève P O, Pradhan S, and Carey M.2007. Functional cooperation between HP1andDNMT1mediates gene silencing. Genes&Development,21(10):1169-1178
Smith S L, Everts R E, Tian X C, Du F, Sung L Y, Rodriguez-Zas S L, Jeong B S, Renard J P, Lewin H A,and Yang X.2005. Global gene expression profiles reveal significant nuclear reprogramming bythe blastocyst stage after cloning. Proc Natl Acad Sci U S A,102(49):17582-1757
Stec I, Nagl S B, van Ommen G J, and den Dunnen J T.2000. The PWWP domain: a potentialprotein-protein interaction domain in nuclear proteins influencing differentiation? Febs Letters,473(1):1-5
Stock A E, and Fortune J E.1993. Ovarian Follicular Dominance in Cattle-Relationship betweenProlonged Growth of the Ovulatory Follicle and Endocrine Parameters. Endocrinology,132(3):1108-1114
Su J M, Wang Y S, Liu Q, Yang B, Wu Y Y, Luo Y, Hu G D, and Zhang Y.2011a. Aberrant mRNAexpression and DNA methylation levels of imprinted genes in cloned transgenic calves that died oflarge offspring syndrome. Livestock Science,141(1):24-35
Su J M, Yang B, Wang Y S, Li Y Y, Xiong X R, Wang L J, Guo Z K, and Zhang Y.2011b. Expression andmethylation status of imprinted genes in placentas of deceased and live cloned transgenic calves.Theriogenology,75(7):1346-1359
Su J, Wang Y, Li Y, Li R, Li Q, Wu Y, Quan F, Liu J, Guo Z, and Zhang Y.2011c. Oxamflatin significantlyimproves nuclear reprogramming, blastocyst quality, and in vitro development of bovine SCNTembryos. Plos One,6(8): e23805
Suemizu H, Aiba K, Yoshikawa T, Sharov A A, Shimozawa N, Tamaoki N, and Ko M S.2003. Expressionprofiling of placentomegaly associated with nuclear transplantation of mouse ES cells.Developmental Biology,253(1):36-53
Sun F L, Dean W L, Kelsey G, Allen N D, and Reik W.1997. Transactivation of Igf2in a mouse model ofBeckwith-Wiedemann syndrome. Nature,389(6653):809-815
Suzuki J, Jr., Therrien J, Filion F, Lefebvre R, Goff A K, Perecin F, Meirelles F V, and Smith L C.2011.Loss of methylation at H19DMD is associated with biallelic expression and reduced developmentin cattle derived by somatic cell nuclear transfer. Biology of Reproduction,84(5):947-956
Suzuki Jr J, Therrien J, Filion F, Lefebvre R, Goff A, Perecin F, Meirelles F, and Smith L.2011. Loss ofmethylation at H19DMD is associated with biallelic expression and reduced development in cattlederived by somatic cell nuclear transfer. Biology of Reproduction,84(5):947-956
Taganov K D, Boldin M P, Chang K J, and Baltimore D.2006. NF-κB-dependent induction of microRNAmiR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proceedings ofthe National Academy of Sciences,103(33):12481-12486
Tahara E, Tahara H, Kanno M, Naka K, Takeda Y, Matsuzaki T, Yamazaki R, Ishihara H, Yasui W, andBarrett J C.2005. G1P3, an interferon inducible gene6-16, is expressed in gastric cancers andinhibits mitochondrial-mediated apoptosis in gastric cancer cell line TMK-1cell. CancerImmunology, Immunotherapy,54(8):729-740
Tahiliani M, Koh K P, Shen Y, Pastor W A, Bandukwala H, Brudno Y, Agarwal S, Iyer L M, Liu D R,Aravind L, and Rao A.2009. Conversion of5-methylcytosine to5-hydroxymethylcytosine inmammalian DNA by MLL partner TET1. Science,324(5929):930-935
Tao H, Suzuki M, Kiyonari H, Abe T, Sasaoka T, and Ueno N.2009. Mouse prickle1, the homolog of aPCP gene, is essential for epiblast apical-basal polarity. Proceedings of the National Academy ofSciences,106(34):14426-14431
Thomson J P, Skene P J, Selfridge J, Clouaire T, Guy J, Webb S, Kerr A R, Deaton A, Andrews R, James KD, Turner D J, Illingworth R, and Bird A.2010. CpG islands influence chromatin structure via theCpG-binding protein Cfp1. Nature,464(7291):1082-1086
Thorvaldsen J L, Duran K L, and Bartolomei M S.1998. Deletion of the H19differentially methylateddomain results in loss of imprinted expression of H19and Igf2. Genes&Development,12(23):3693-3702
Tian X C, Kubota C, Enright B, and Yang X.2003. Cloning animals by somatic cell nucleartransfer--biological factors. Reprod Biol Endocrinol,1:98
Tian X C, Xu J, and Yang X Z.2000. Normal telomere lengths found in cloned cattle. Nature Genetics,26(3):272-273
Torner H, Ghanem N, Ambros C, Holker M, Tomek W, Phatsara C, Alm H, Sirard M A, Kanitz W,Schellander K, and Tesfaye D.2008. Molecular and subcellular characterisation of oocytesscreened for their developmental competence based on glucose-6-phosphate dehydrogenaseactivity. Reproduction,135(2):197-212
Tremblay K D, Duran K L, and Bartolomei M S.1997. A5'2-kilobase-pair region of the imprinted mouseH19gene exhibits exclusive paternal methylation throughout development. Molecular andCellular Biology,17(8):4322-4329
Urabe A.1994. Interferons for the treatment of hematological malignancies. Oncology,51(2):137-141
Valinluck V, and Sowers L C.2007. Endogenous cytosine damage products alter the site selectivity ofhuman DNA maintenance methyltransferase DNMT1. Cancer Research,67(3):946-950
Van Thuan N, Bui H T, Kim J H, Hikichi T, Wakayama S, Kishigami S, Mizutani E, and Wakayama T.2009. The histone deacetylase inhibitor scriptaid enhances nascent mRNA production and rescuesfull-term development in cloned inbred mice. Reproduction,138(2):309-317
Vassena R, Han Z, Gao S, Baldwin D A, Schultz R M, and Latham K E.2007. Tough beginnings:alterations in the transcriptome of cloned embryos during the first two cell cycles. DevelopmentalBiology,304(1):75-89
Vassena R, Mapletoft R J, Allodi S, Singh J, and Adams G P.2003. Morphology and developmentalcompetence of bovine oocytes relative to follicular status. Theriogenology,60(5):923-932
Vucic E A, Wilson I M, Campbell J M, and Lam W L.2009. Methylation Analysis by DNAImmunoprecipitation(MeDIP). Methods in Molecular Biology,556:141-153
Wakayama T, Perry A C F, Zuccotti M, Johnson K R, and Yanagimachi R.1998. Full-term development ofmice from enucleated oocytes injected with cumulus cell nuclei. Nature,394(6691):369-374
Wakayama T, and Yanagimachi R.2001. Mouse cloning with nucleus donor cells of different age and type.Molecular Reproduction and Development,58(4):376-383
Wang L J, Zhang H, Wang Y S, Xu W B, Xiong X R, Li Y Y, Su J M, Hua S, and Zhang Y.2011a. ScriptaidImproves In Vitro Development and Nuclear Reprogramming of Somatic Cell Nuclear TransferBovine Embryos. Cellular Reprogramming,13(5):431-439
Wang S, Aurora A B, Johnson B A, Qi X, McAnally J, Hill J A, Richardson J A, Bassel-Duby R, and OlsonE N.2008. The endothelial-specific microRNA miR-126governs vascular integrity andangiogenesis. Developmental Cell,15(2):261-271
Wang Y, Medvid R, Melton C, Jaenisch R, and Blelloch R.2007. DGCR8is essential for microRNAbiogenesis and silencing of embryonic stem cell self-renewal. Nature Genetics,39(3):380-385
Wang Y, Liu J, Tang S, An Z, Guo Z, Ding X, Liu F, Cao Z, Zhang T, and Zhang Y.2009. Modifications ofchemically induced-enucleated nuclear transfer technique by reverse-order nuclear transfer inmouse. Zygote,17(3):261-268
Wang Y, Su J, Wang L, Xu W, Quan F, Liu J, and Zhang Y.2011b. The Effects of5-Aza-2'-Deoxycytidineand Trichostatin A on Gene Expression and DNA Methylation status in Cloned Bovine Blastocysts.Cellular Reprogramming,13(4):297-306
Wang Y S, Tang S, An Z X, Li W Z, Liu J, Quan F S, Hua S, and Zhang Y.2011c. Effect of mSOF andG1.1/G2.2Media on the Developmental Competence of SCNT-Derived Bovine Embryos.Reproduction in Domestic Animals,46(3):404-409
Wang Y S, Xiong X R, An Z X, Wang L J, Liu J, Quan F S, Hua S, and Zhang Y.2011d. Production ofcloned calves by combination treatment of both donor cells and early cloned embryos with5-aza-2′-deoxycytidine and trichostatin A. Theriogenology,75(5):819–825
Wang Y S, Zhao X, Su J M, An Z X, Xiong X R, Wang L J, Liu J, Quan F S, Hua S, and Zhang Y.2011e.Lowering storage temperature during ovary transport is beneficial to the developmentalcompetence of bovine oocytes used for somatic cell nuclear transfer. Animal Reproduction Science,124(1-2):48-54
Warzych E, Peippo J, Szydlowski M, and Lechniak D.2007. Supplements to in vitro maturation mediaaffect the production of bovine blastocysts and their apoptotic index but not the proportions ofmatured and apoptotic oocytes. Animal Reproduction Science,97(3-4):334-343
Weber M, Davies J J, Wittig D, Oakeley E J, Haase M, Lam W L, and Schübeler D.2005.Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylationin normal and transformed human cells. Nature Genetics,37(8):853-862
Weber M, Hellmann I, Stadler M B, Ramos L, P bo S, Rebhan M, and Schübeler D.2007. Distribution,silencing potential and evolutionary impact of promoter DNA methylation in the human genome.Nature Genetics,39(4):457-466
Wee G, Shim J J, Koo D B, Chae J I, Lee K K, and Han Y M.2007. Epigenetic alteration of the donor cellsdoes not recapitulate the reprogramming of DNA methylation in cloned embryos. Reproduction,134(6):781-787
Wei Y C, Zhu J, Huan Y J, Liu Z F, Yang C R, Zhang X M, Mu Y S, Xia P, and Liu Z H.2010. AberrantExpression and Methylation Status of Putatively Imprinted Genes in Placenta of Cloned Piglets.Cellular Reprogramming,12(2):213-222
Wightman B, Ha I, and Ruvkun G.1993. Posttranscriptional regulation of the heterochronic gene lin-14bylin-4mediates temporal pattern formation in C. elegans. Cell,75(5):855-862
Wilmut I, Beaujean N, de Sousa P A, Dinnyes A, King T J, Paterson L A, Wells D N, and Young L E.2002.Somatic cell nuclear transfer. Nature,419(6907):583-586
Wilmut I, Schnieke A E, McWhir J, Kind A J, and Campbell K H S.1997. Viable offspring derived fromfetal and adult mammalian cell. Nature,386(6619):810-813
Willinger T, Freeman T, Herbert M, Hasegawa H, McMichael A J, and Callan M F C.2006. Human naiveCD8T cells down-regulate expression of the WNT pathway transcription factors lymphoidenhancer binding factor1and transcription factor7(T cell factor-1) following antigen encounterin vitro and in vivo. The Journal of Immunology,176(3):1439-1446
Woods G L, White K L, Vanderwall D K, Li G P, Aston K I, Bunch T D, Meerdo L N, and Pate B J.2003.A mule cloned from fetal cells by nuclear transfer. Science,301(5636):1063-1063
Wossidlo M, Nakamura T, Lepikhov K, Marques C J, Zakhartchenko V, Boiani M, Arand J, Nakano T,Reik W, and Walter J.2011.5-Hydroxymethylcytosine in the mammalian zygote is linked withepigenetic reprogramming. Nature Communications,2:241
Wrenzycki C, Lucas-Hahn A, Herrmann D, Lemme E, Korsawe K, and Niemann H.2002b. In vitroproduction and nuclear transfer affect dosage compensation of the X-linked gene transcripts G6PD,PGK, and Xist in preimplantation bovine embryos. Biology of Reproduction,66(1):127-134
Wu J Q, Seay M, Schulz V P, Hariharan M, Tuck D, Lian J, Du J, Shi M, Ye Z, and Gerstein M.2012. Tcf7Is an Important Regulator of the Switch of Self-Renewal and Differentiation in a MultipotentialHematopoietic Cell Line. Plos Genetics,8(3): e1002565
Wu H, and Zhang Y.2011a. Mechanisms and functions of Tet protein-mediated5-methylcytosine oxidation.Genes Dev,25(23):2436-2452
Wu H, and Zhang Y.2011b. Tet1and5-hydroxymethylation: A genome-wide view in mouse embryonicstem cells. Cell Cycle,10(15):2428-2436
Wu S C, and Zhang Y.2010. Active DNA demethylation: many roads lead to Rome. Nat Rev Mol Cell Biol,11(9):607-620
Wu Y G, Liu Y, Zhou P, Lan G C, Han D, Miao D Q, and Tan J H.2007. Selection of oocytes for in vitromaturation by brilliant cresyl blue staining: a study using the mouse model. Cell Research,17(8):722-731
Xia H, Qi Y, Ng S S, Chen X, Li D, Chen S, Ge R, Jiang S, Li G, and Chen Y.2009. microRNA-146binhibits glioma cell migration and invasion by targeting MMPs. Brain Research,1269:158-165
Xu W, Yang H, Liu Y, Yang Y, Wang P, Kim S H, Ito S, Yang C, and Xiao M T.2011. Oncometabolite2-Hydroxyglutarate Is a Competitive Inhibitor of [alpha]-Ketoglutarate-Dependent Dioxygenases.Cancer Cell,19(1):17-30
Xue F, Tian X C, Du F, Kubota C, Taneja M, Dinnyes A, Dai Y, Levine H, Pereira L V, and Yang X.2002.Aberrant patterns of X chromosome inactivation in bovine clones. Nat Genet,31(2):216-220
Yamanaka K, Sugimura S, Wakai T, Kawahara M, and Sato E.2009. Acetylation Level of Histone H3inEarly Embryonic Stages Affects Subsequent Development of Miniature Pig Somatic Cell NuclearTransfer Embryos. Journal of Reproduction and Development,55(6):638-644
Yang C R, Miao D Q, Zhang Q H, Guo L, Tong J S, Wei Y, Huang X, Hou Y, Schatten H, Liu Z, and Sun QY.2010. Short-term preservation of porcine oocytes in ambient temperature: novel approaches.Plos One,5(12): e14242
Yang F K, Hao R, Kessler B, Brem G, Wolf E, and Zakhartchenko V.2007a. Rabbit somatic cell cloning:effects of donor cell type, histone acetylation status and chimeric embryo complementation.Reproduction,133(1):219-230
Yang L, Chavatte-Palmer P, Kubota C, O'Neill M, Hoagland T, Renard J P, Taneja M, Yang X Z, and TianX C.2005. Expression of imprinted genes is aberrant in deceased newborn cloned calves andrelatively normal in surviving adult clones. Molecular Reproduction and Development,71(4):431-438
Yang X, Feng M, Jiang X, Wu Z, Li Z, Aau M, and Yu Q.2009. miR-449a and miR-449b are directtranscriptional targets of E2F1and negatively regulate pRb–E2F1activity through a feedback loopby targeting CDK6and CDC25A. Genes&Development,23(20):2388-2393
Yang X, and Seto E.2007. HATs and HDACs: from structure, function and regulation to novel strategiesfor therapy and prevention. Oncogene,26(37):5310-5318
Yang X J, and Seto E.2008. The Rpd3/Hda1family of lysine deacetylases: from bacteria and yeast to miceand men. Nature Reviews Molecular Cell Biology,9(3):206-218
Yang X Z, Smith S L, Tian X C, Lewin H A, Renard J P, and Wakayama T.2007b. Nuclear reprogrammingof cloned embryos and its implications for therapeutic cloning. Nature Genetics,39(3):295-302
Young L E, Fernandes K, McEvoy T G, Butterwith S C, Gutierrez C G, Carolan C, Broadbent P J,Robinson J J, Wilmut I, and Sinclair K D.2001. Epigenetic change in IGF2R is associated withfetal overgrowth after sheep embryo culture. Nature Genetics,27(2):153-154
Yeh E T H.2009. SUMOylation and De-SUMOylation: wrestling with life's processes. Journal ofBiological Chemistry,284(13):8223-8227
Zawada W M, Cibelli J B, Choi P K, Clarkson E D, Golueke P J, Witta S E, Bell K P, Kane J, de Leon F AP, Jerry D J, Robl J M, Freed C R, and Stice S L.1998. Somatic cell cloned transgenic bovineneurons for transplantation in parkinsonian rats. Nature Medicine,4(5):569-574
Zemach A, McDaniel I E, Silva P, and Zilberman D.2010. Genome-wide evolutionary analysis ofeukaryotic DNA methylation. Science,328(5980):916-919
Zhang M, Wang F C, Kou Z H, Zhang Y, and Gao S R.2009. Defective Chromatin Structure in SomaticCell Cloned Mouse Embryos. Journal of Biological Chemistry,284(37):24981-24987
Zhang X, Yazaki J, Sundaresan A, Cokus S, Chan S W L, Chen H, Henderson I R, Shinn P, Pellegrini M,and Jacobsen S E.2006. Genome-wide high-resolution mapping and functional analysis of DNAmethylation in Arabidopsis. Cell,126(6):1189-1201
Zhang Y H, Li J, Villemoes K, Pedersen A M, Purup S, and Vajta G.2007. An epigenetic modifier results inimproved in vitro blastocyst production after somatic cell nuclear transfer. Cloning and Stem Cells,9(3):357-363
Zhao J, Hao Y, Ross J W, Spate L D, Walters E M, Samuel M S, Rieke A, Murphy C N, and Prather R S.2010. Histone deacetylase inhibitors improve in vitro and in vivo developmental competence ofsomatic cell nuclear transfer porcine embryos. Cellular Reprogramming,12(1):75-83
Zhao J G, Ross J W, Hao Y H, Spate L D, Walters E M, Samuel M S, Rieke A, Murphy C N, and Prather RS.2009. Significant Improvement in Cloning Efficiency of an Inbred Miniature Pig by HistoneDeacetylase Inhibitor Treatment after Somatic Cell Nuclear Transfer. Biology of Reproduction,81(3):525-530
Zhou Q, Chipperfield H, Melton D A, and Wong W H.2007. A gene regulatory network in mouseembryonic stem cells. Proceedings of the National Academy of Sciences,104(42):16438-16443
Zhou Q, Renard J P, Le Friec G, Brochard V, Beaujean N, Cherifi Y, Fraichard A, and Cozzi J.2003.Generation of fertile cloned rats by regulating oocyte activation. Science,302(5648):1179-1179
Zhou W, Xiang T, Walker S, Farrar V, Hwang E, Findeisen B, Sadeghieh S, Arenivas F, Abruzzese R V, andPolejaeva I.2008. Global gene expression analysis of bovine blastocysts produced by multiplemethods. Molecular Reproduction and Development,75(5):744-58
Zuccotti M, and Monk M.1995. Methylation of the Mouse Xist Gene in Sperm and Eggs Correlates withImprinted Xist Expression and Paternal X-Inactivation. Nature Genetics,9(3):316-320
Aguilar A L, Piskol R, Beitzinger M, Zhu J Y, Kruspe D, Aszodi A, Moser M, Englert C, and Meister G.2010. The small RNA expression profile of the developing murine urinary and reproductivesystems. Febs Letters,584(21):4426-4434
Akagi S, Adachi N, Matsukawa K, Kubo M, and Takahashi S.2003. Developmental potential of bovinenuclear transfer embryos and postnatal survival rate of cloned calves produced by two differenttimings of fusion and activation. Molecular Reproduction and Development,66(3):264-272
Al-Katanani Y M, Paula-Lopes F F, and Hansen P J.2002. Effect of season and exposure to heat stress onoocyte competence in Holstein cows. Journal of Dairy Science,85(2):390-396
Allfrey V, Faulkner R, and Mirsky A.1964. Acetylation and methylation of histones and their possible rolein the regulation of RNA synthesis. Proceedings of the National Academy of Sciences of theUnited States of America,51(5):786
Alm H, Torner H, Lohrke B, Viergutz T, Ghoneim I M, and Kanitz W.2005. Bovine blastocystdevelopment rate in vitro is influenced by selection of oocytes by brillant cresyl blue stainingbefore IVM as indicator for glucose-6-phosphate dehydrogenase activity. Theriogenology,63(8):2194-2205
Anderlind C, Spira A, Cardoso W V, and Lü J.2010. miR-129regulates cell proliferation bydownregulating Cdk6expression. Cell Cycle,9(9):1809-1818
Arat S, Gibbons J, Rzucidlo S J, Respess D S, Tumlin M, and Stice S L.2002. In vitro development ofbovine nuclear transfer embryos from transgenic clonal lines of adult and fetal fibroblast cells ofthe same genotype. Biology of Reproduction,66(6):1768-1774
Ariel M, Robinson E, Mccarrey J R, and Cedar H.1995. Gamete-Specific Methylation Correlates withImprinting of the Murine Xist Gene. Nature Genetics,9(3):312-315
Arnold D R, Fortier A L, Lefebvre R, Miglino M A, Pfarrer C, and Smith L C.2008. Placentalinsufficiencies in cloned animals-a workshop report. Placenta,29Suppl A: S108-S110
Aston K I, Li G P, Hicks B A, Sessions B R, Davis A P, Rickords L F, Stevens J R, and White K L.2010.Abnormal Levels of Transcript Abundance of Developmentally Important Genes in Various Stagesof Preimplantation Bovine Somatic Cell Nuclear Transfer Embryos. Cellular Reprogramming,12(1):23-32
Audic S, and Claverie J M.1997. The significance of digital gene expression profiles. Genome Research,7(10):986-995
Baguisi A, Behboodi E, Melican D T, Pollock J S, Destrempes M M, Cammuso C, Williams J L, Nims S D,Porter C A, Midura P, Palacios M J, Ayres S L, Denniston R S, Hayes M L, Ziomek C A, Meade HM, Godke R A, Gavin W G, Overstrom E W, and Echelard Y.1999. Production of goats by somaticcell nuclear transfer. Nature Biotechnology,17(5):456-461
Bartel D P.2004. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell,116(2):281-297
Beard C, Li E, and Jaenisch R.1995. Loss of methylation activates Xist in somatic but not in embryoniccells. Genes Dev,9(19):2325-2334
Bedford M T, and Clarke S G.2009. Protein arginine methylation in mammals: who, what, and why.Molecular Cell,33(1):1-13
Beebe L F S, Mcllfatrick S J, and Nottle M B.2009. Cytochalasin B and Trichostatin A TreatmentPostactivation Improves In Vitro Development of Porcine Somatic Cell Nuclear Transfer Embryos.Cloning and Stem Cells,11(4):477-482
Benjamini Y, and Yekutieli D.2001. The control of the false discovery rate in multiple testing underdependency. Annals of statistics,29(4):1165-1188
Berg D K, Smith C S, Pearton D J, Wells D N, Broadhurst R, Donnison M, and Pfeffer P L.2011.Trophectoderm Lineage Determination in Cattle. Developmental Cell,20(2):244-255
Bermejo-Alvarez P, Ramos-Ibeas P, and Gutierrez-Adan A.2012. Solving the "x" in embryos and stemcells. Stem Cells Dev,21(8):1215-1224
Beyhan Z, Forsberg E J, Eilertsen K J, Kent-First M, and First N L.2007. Gene expression in bovinenuclear transfer embryos in relation to donor cell efficiency in producing live offspring. MolecularReproduction and Development,74(1):18-27
Bhojwani S, Alm H, Torner H, Kanitz W, and Poehland R.2007. Selection of developmentally competentoocytes through brilliant cresyl blue stain enhances blastocyst development rate after bovinenuclear transfer. Theriogenology,67(2):341-345
Bischoff S R, Tsai S, Hardison N, Motsinger-Reif A A, Freking B A, Nonneman D, Rohrer G, andPiedrahita J A.2009. Characterization of Conserved and Nonconserved Imprinted Genes in Swine.Biology of Reproduction,81(5):906-920
Blackwell L, Norris J, Suto C M, and Janzen W P.2008. The use of diversity profiling to characterizechemical modulators of the histone deacetylases. Life Sciences,82(21):1050-1058
Blondin P, Bousquet D, Twagiramungu H, Barnes F, and Sirard M A.2002. Manipulation of folliculardevelopment to produce developmentally competent bovine oocytes. Biology of Reproduction,66(1):38-43
Bock C, Reither S, Mikeska T, Paulsen M, Walter J, and Lengauer T.2005. BiQ analyzer: visualization andquality control for DNA methylation data from bisulfite sequencing. Bioinformatics,21(21):4067-4068
Borden E C, Lindner D, Dreicer R, Hussein M, and Peereboom D.(2000). Second-generation interferonsfor cancer: clinical targets.Seminars in Cancer Biology,10(2):125-144
Bostick M, Kim J K, Esteve P O, Clark A, Pradhan S, and Jacobsen S E.2007. UHRF1plays a role inmaintaining DNA methylation in mammalian cells. Science,317(5845):1760-1764
Brennecke J, Stark A, Russell R B, and Cohen S M.2005. Principles of microRNA-target recognition. PlosBiology,3(3): e85
Bui H T, Wakayama S, Kishigami S, Park K K, Kim J H, Thuan N V, and Wakayama T.2010. Effect oftrichostatin A on chromatin remodeling, histone modifications, DNA replication, andtranscriptional activity in cloned mouse embryos. Biology of Reproduction,83(3):454-63
Buscaglia L E, and Li Y.2011. Apoptosis and the target genes of microRNA-21. Chin J Cancer,30(6):371-80
Campbell K H, McWhir J, Ritchie W A, and Wilmut I.1996. Sheep cloned by nuclear transfer from acultured cell line. Nature,380(6569):64-66
Campbell K H S, Fisher P, Chen W C, Choi I, Kelly R D W, Lee J H, and Xhu J.2007. Somatic cellnuclear transfer: Past, present and future perspectives. Theriogenology,68Suppl1: S214-S231
Carreira-Barbosa F, Concha M L, Takeuchi M, Ueno N, Wilson S W, and Tada M.2003. Prickle1regulatescell movements during gastrulation and neuronal migration in zebrafish. Development,130(17):4037-4046
Castro F, Sharbati S, Rodriguez-Alvarez L, Cox J, Hultschig C, and Einspanier R.2010. MicroRNAexpression profiling of elongated cloned and in vitro-fertilized bovine embryos. Theriogenology,73(1):71-85
Catala M G, Izquierdo D, Uzbekova S, Morato R, Roura M, Romaguera R, Papillier P, and Paramio M T.2011. Brilliant Cresyl Blue stain selects largest oocytes with highest mitochondrial activity,maturation-promoting factor activity and embryo developmental competence in prepubertal sheep.Reproduction,142(4):517-27
Cervera R P, Silvestre M A, Marti N, Garcia-Mengual E, Moreno R, and Stojkovic M.2010. Effects ofdifferent oocyte activation procedures on development and gene expression of porcinepre-implantation embryos. Reproduction in Domestic Animals,45(5): e12-20
Chan J A, Krichevsky A M, and Kosik K S.2005. MicroRNA-21is an antiapoptotic factor in humanglioblastoma cells. Cancer Research,65(14):6029-6033
Chavatte-Palmer P, Heyman Y, Richard C, Monget P, LeBourhis D, Kann G, Chilliard Y, Vignon X, andRenard J.2002a. Clinical, hormonal, and hematologic characteristics of bovine calves derivedfrom nuclei from somatic cells. Biology of Reproduction,66(6):1596-1603
Chen T P, Tsujimoto N, and Li E.2004. The PWWP domain of Dnmt3a and Dnmt3b is required fordirecting DNA methylation to the major satellite repeats at pericentric heterochromatin. Molecularand Cellular Biology,24(20):9048-9058
Cheriyath V, Glaser K B, Waring J F, Baz R, Hussein M A, and Borden E C.2007. G1P3, an IFN-inducedsurvival factor, antagonizes TRAIL-induced apoptosis in human myeloma cells. Journal ofClinical Investigation,117(10):3107-3117
Chesne P, Adenot P G, Viglietta C, Baratte M, Boulanger L, and Renard J P.2002. Cloned rabbits producedby nuclear transfer from adult somatic cells. Nature Biotechnology,20(4):366-369
Chiyomaru T, Enokida H, Tatarano S, Kawahara K, Uchida Y, Nishiyama K, Fujimura L, Kikkawa N, SekiN, and Nakagawa M.2010. miR-145and miR-133a function as tumour suppressors and directlyregulate FSCN1expression in bladder cancer. British Journal of Cancer,102(5):883-891
Cokus S J, Feng S, Zhang X, Chen Z, Merriman B, Haudenschild C D, Pradhan S, Nelson S F, PellegriniM, and Jacobsen S E.2008. Shotgun bisulphite sequencing of the Arabidopsis genome revealsDNA methylation patterning. Nature,452(7184):215-219
Constant F, Guillomot M, Heyman Y, Vignon X, Laigre P, Servely J L, Renard J P, and Chavatte-Palmer P.2006. Large offspring or large placenta syndrome? Morphometric analysis of late gestation bovineplacentomes from somatic nuclear transfer pregnancies complicated by hydrallantois. Biology ofReproduction,75(1):122-130
Cortázar D, Kunz C, Selfridge J, Lettieri T, Saito Y, MacDougall E, Wirz A, Schuermann D, Jacobs A L,and Siegrist F.2011. Embryonic lethal phenotype reveals a function of TDG in maintainingepigenetic stability. Nature,470(7334):419-423
Cortellino S, Xu J, Sannai M, Moore R, Caretti E, Cigliano A, LeáCoz M, Devarajan K, Wessels A, andSoprano D.2011. Thymine DNA glycosylase is essential for active DNA demethylation by linkeddeamination-base excision repair. Cell,146(1):67-79
Costa-Borges N, Santalo J, and Ibanez E.2010. Comparison between the Effects of Valproic Acid andTrichostatin A on the In Vitro Development, Blastocyst Quality, and Full-Term Development ofMouse Somatic Cell Nuclear Transfer Embryos. Cellular Reprogramming,12(4):437-446
Cui X S, Zhang D X, Ko Y G, and Kim N H.2009. Aberrant epigenetic reprogramming of imprintedmicroRNA-127and Rtl1in cloned mouse embryos. Biochem Biophys Res Commun,379(2):390-394
Cui X S, Xu Y N, Shen X H, Zhang L Q, Zhang J B, and Kim N H.2011. Trichostatin A modulatesapoptotic-related gene expression and improves embryo viability in cloned bovine embryos.Cellular Reprogramming,13(2):179-189
Curchoe C L, Zhang S Q, Yang L, Page R, and Tian X C.2009. Hypomethylation trends in the intergenicregion of the imprinted IGF2and H19genes in cloned cattle. Animal Reproduction Science,116(3-4):213-225
Dai X P, Hao J, Hou X J, Hai T, Fan Y, Yu Y, Jouneau A, Wang L, and Zhou Q.2010. Somatic NucleusReprogramming Is Significantly Improved by m-Carboxycinnamic Acid Bishydroxamide, aHistone Deacetylase Inhibitor. Journal of Biological Chemistry,285(40):31002-31010
Das Z C, Gupta M K, Uhm S J, and Lee H T.2010. Increasing histone acetylation of cloned embryos, butnot donor cells, by sodium butyrate improves their in vitro development in pigs. CellularReprogramming,12(1):95-104
Dawson M A, Bannister A J, G ttgens B, Foster S D, Bartke T, Green A R, and Kouzarides T.2009. JAK2phosphorylates histone H3Y41and excludes HP1&agr; from chromatin. Nature,461(7265):819-822
De Sousa P A, King T, Harkness L, Young L E, Walker S K, and Wilmut I.2001. Evaluation of gestationaldeficiencies in cloned sheep fetuses and placentae. Biology of Reproduction,65(1):23-30
Dean W, Santos F, and Reik W.(2003). Epigenetic reprogramming in early mammalian development andfollowing somatic nuclear transfer. Semin Cell Dev Biol,14(1):93-100
Dean W, Santos F, Stojkovic M, Zakhartchenko V, Walter J, Wolf E, and Reik W.2001. Conservation ofmethylation reprogramming in mammalian development: Aberrant reprogramming in clonedembryos. Proceedings of the National Academy of Sciences of the United States of America,98(24):13734-13738
Delcuve G P, Rastegar M, and Davie J R.2009. Epigenetic control. Journal of Cellular Physiology,219(2):243-250
Deshmukh R S, strup O, strup E, Vejlsted M, Niemann H, Lucas-Hahn A, Petersen B, Li J, Callesen H,and Hyttel P.2011. DNA methylation in porcine preimplantation embryos developed in vivo andproduced by in vitro fertilization, parthenogenetic activation and somatic cell nuclear transfer.Epigenetics,6(2):177-187
Ding X, Wang Y, Zhang D, Wang Y, Guo Z, and Zhang Y.2008. Increased pre-implantation developmentof cloned bovine embryos treated with5-aza-2'-deoxycytidine and trichostatin A. Theriogenology,70(4):622-630
Dong G E, Luo J, Kumar V, and Dong Z.2010. Inhibitors of histone deacetylases suppresscisplatin-induced p53activation and apoptosis in renal tubular cells. American Journal ofPhysiology-Renal Physiology,298(2):293-300
Dovey O M, Foster C T, and Cowley S M.2010. Histone deacetylase1(HDAC1), but not HDAC2,controls embryonic stem cell differentiation. Proceedings of the National Academy of Sciences,107(18):8242-8247
Easwaran H P, Schermelleh L, Leonhardt H, and Cardoso M C.2004. Replication-independent chromatinloading of Dnmt1during G2and M phases. Embo Reports,5(12):1181-1186
Eckhardt F, Lewin J, Cortese R, Rakyan V K, Attwood J, Burger M, Burton J, Cox T V, Davies R, andDown T A.2006. DNA methylation profiling of human chromosomes6,20and22. NatureGenetics,38(12):1378-1385
Eggan K, Akutsu H, Hochedlinger K, Rideout W,3rd, Yanagimachi R, and Jaenisch R.2000.X-Chromosome inactivation in cloned mouse embryos. Science,290(5496):1578-1581
Esau C, Davis S, Murray S F, Yu X X, Pandey S K, Pear M, Watts L, Booten S L, Graham M, and McKayR.2006. miR-122regulation of lipid metabolism revealed by in vivo antisense targeting. CellMetabolism,3(2):87-98
Escamilla-Del-Arenal M, da Rocha S T, and Heard E.2011. Evolutionary diversity and developmentalregulation of X-chromosome inactivation. Hum Genet,130(2):307-327
Estève P O, Chin H G, Smallwood A, Feehery G R, Gangisetty O, Karpf A R, Carey M F, and Pradhan S.2006. Direct interaction between DNMT1and G9a coordinates DNA and histone methylationduring replication. Genes&Development,20(22):3089-3103
Esteves T C, Balbach S T, Pfeiffer M J, Arauzo-Bravo M J, Klein D C, Sinn M, and Boiani M.2011.Somatic cell nuclear reprogramming of mouse oocytes endures beyond reproductive decline.Aging Cell,10(1):80-95
Ficz G, Branco M R, Seisenberger S, Santos F, Krueger F, Hore T A, Marques C J, Andrews S, and Reik W.2011. Dynamic regulation of5-hydroxymethylcytosine in mouse ES cells and duringdifferentiation. Nature,473(7347):398-402
Fish J E, Santoro M M, Morton S U, Yu S, Yeh R F, Wythe J D, Ivey K N, Bruneau B G, Stainier D Y R,and Srivastava D.2008. miR-126regulates angiogenic signaling and vascular integrity.Developmental Cell,15(2):272-284
Fouladi-Nashta A A, Gutierrez C G, Gong J G, Garnsworthy P C, and Webb R.2007. Impact of dietary fattyacids on oocyte quality and development in lactating dairy cows. Biology of Reproduction,77(1):9-17
Fu Y F, Du T T, Dong M, Zhu K Y, Jing C B, Zhang Y, Wang L, Fan H B, Chen Y, and Jin Y.2009. mir-144selectively regulates embryonic α-hemoglobin synthesis during primitive erythropoiesis. Blood,113(6):1340-1349
Fukuda A, Cao F, Morita S, Yamada K, Jincho Y, Tane S, Sotomaru Y, and Kono T.2010. Identification ofinappropriately reprogrammed genes by large-scale transcriptome analysis of individual clonedmouse blastocysts. Plos One,5(6): e11274
Galli C, Lagutina I, Crotti G, Colleoni S, Turini P, Ponderato N, Duchi R, and Lazzari G.2003. A clonedhorse born to its dam twin (vol424, pg635,2003). Nature,425(6959):680-680
Gardiner-Garden M, and Frommer M.1987. CpG islands in vertebrate genomes. Journal of MolecularBiology,196(2):261-282
Ge Y Z, Pu M T, Gowher H, Wu H P, Ding J P, Jeltsch A, and Xu G L.2004. Chromatin targeting of denovo DNA methyltransferases by the PWWP domain. Journal of Biological Chemistry,279(24):25447-25454
Gicquel C, Rossignol S, Cabrol S, Houang M, Steunou V, Barbu V, Danton F, Thibaud N, Le Merrer M,Burglen L, Bertrand A M, Netchine I, and Le Bouc Y.2005. Epimutation of the telomericimprinting center region on chromosome11p15in Silver-Russell syndrome. Nature Genetics,37(9):1003-1007
Gill G.2003. Post-translational modification by the small ubiquitin-related modifier SUMO has big effectson transcription factor activity. Current Opinion in Genetics&Development,13(2):108-113
Glazov E A, Kongsuwan K, Assavalapsakul W, Horwood P F, Mitter N, and Mahony T J.2009. Repertoireof bovine miRNA and miRNA-like small regulatory RNAs expressed upon viral infection. PlosOne,4(7): e6349
Gong G, Dai Y, Fan B, Zhu H, Wang H, Wang L, and Fang C.2004. Production of transgenic blastocystsby nuclear transfer from different types of somatic cells in cattle. Sci China Ser C,47(1):83–189
Gopichandran N, and Leese H J.2006. The effect of paracrine/autocrine interactions on the in vitro cultureof bovine preimplantation embryos. Reproduction,131(2):269-277
Gore A, Li Z, Fung H L, Young J E, Agarwal S, Antosiewicz-Bourget J, Canto I, Giorgetti A, Israel M A,Kiskinis E, Lee J H, Loh Y H, Manos P D, Montserrat N, Panopoulos A D, Ruiz S, Wilbert M L,Yu J Y, Kirkness E F, Belmonte J C I, Rossi D J, Thomson J A, Eggan K, Daley G Q, Goldstein LS B, and Zhang K.2011. Somatic coding mutations in human induced pluripotent stem cells.Nature,471(7336):63-76
Gottipati S, Rao N L, and Fung-Leung W P.2008. IRAK1: a critical signaling mediator of innate immunity.Cellular signalling,20(2):269-276
Grunder E, D'Ambrosio R, Fiaschetti G, Abela L, Arcaro A, Zuzak T, Ohgaki H, Lv S Q, Shalaby T, andGrotzer M.2011. MicroRNA-21suppression impedes medulloblastoma cell migration. EuropeanJournal of Cancer,47(16):2479-2490
Gu T P, Guo F, Yang H, Wu H P, Xu G F, Liu W, Xie Z G, Shi L, He X, Jin S G, Iqbal K, Shi Y G, Deng Z,Szabo P E, Pfeifer G P, Li J, and Xu G L.2011. The role of Tet3DNA dioxygenase in epigeneticreprogramming by oocytes. Nature,477(7366):606-610
Gu Z, Eleswarapu S, and Jiang H.2007. Identification and characterization of microRNAs from the bovineadipose tissue and mammary gland. Febs Letters,581(5):981-988
GuangXian X, Yan Z, Hao J, Juan L, XiaoMing L, Engelhardt J, and YuJiong W.2009. Cloning andidentification of microRNAs in bovine alveolar macrophages. Molecular and CellularBiochemistry,332(1/2):9-16
Hajkova P, Erhardt S, Lane N, Haaf T, El-Maarri O, Reik W, Walter J, and Surani M A.2002. Epigeneticreprogramming in mouse primordial germ cells. Mech Dev,117(1-2):15-23
Han D W, Song S J, Uhum S J, Do J T, Kim N H, Chung K S, and Lee H T.2003. Expression of IGF2andIGF receptor mRNA in bovine nuclear transferred embryos. Zygote,11(3):245-252
Han J, Lee Y, Yeom K H, Kim Y K, Jin H, and Kim V N.2004. The Drosha-DGCR8complex in primarymicroRNA processing. Genes&Development,18(24):3016-3027
Hark A T, Schoenherr C J, Katz D J, Ingram R S, Levorse J M, and Tilghman S M.2000. CTCF mediatesmethylation-sensitive enhancer-blocking activity at the H19/Igf2locus. Nature,405(6785):486-489
He Y F, Li B Z, Li Z, Liu P, Wang Y, Tang Q, Ding J, Jia Y, Chen Z, Li L, Sun Y, Li X, Dai Q, Song C X,Zhang K, He C, and Xu G L.2011. Tet-mediated formation of5-carboxylcytosine and its excisionby TDG in mammalian DNA. Science,333(6047):1303-1307
Hill J R, Edwards J F, Sawyer N, Blackwell C, and Cibelli J B.2001. Placental anomalies in a viablecloned calf. Cloning,3(2):83-88
Hill J R, Winger Q A, Long C R, Looney C R, Thompson J A, and Westhusin M E.2000. Developmentrates of male bovine nuclear transfer embryos derived from adult and fetal cells. Biology ofReproduction,62(5):1135-1140
Himaki T, Yokomine T A, Sato M, Takao S, Miyoshi K, and Yoshida M.2010. Effects of trichostatin A onin vitro development and transgene function in somatic cell nuclear transfer embryos derived fromtransgenic Clawn miniature pig cells. Animal Science Journal,81(5):558-563
Hochedlinger K, and Plath K.2009. Epigenetic reprogramming and induced pluripotency. Development,136(4):509-523
Hodawadekar S, and Marmorstein R.2007. Chemistry of acetyl transfer by histone modifying enzymes:structure, mechanism and implications for effector design. Oncogene,26(37):5528-5540
Holmgren C, Kanduri C, Dell G, Ward A, Mukhopadhya R, Kanduri M, Lobanenkov V, and Ohlsson R.2001. CpG methylation regulates the Igf2/H19insulator. Current Biology,11(14):1128-1130
Holmberg J, Armulik A, Senti K A, Edoff K, Spalding K, Momma S, Cassidy R, Flanagan J G, and Frisén J.2005. Ephrin-A2reverse signaling negatively regulates neural progenitor proliferation andneurogenesis. Genes&Development,19(4):462-471
Hong Y, Yang J, Chi Y, Wang W, Wu W, Yun X, Kong X, and Gu J.2010. BCL2L12A localizes to the cellnucleus and induces growth inhibition through G2/M arrest in CHO cells. Molecular and CellularBiochemistry,333(1):323-330
Hu S, Xie Z, Onishi A, Yu X, Jiang L, Lin J, Rho H, and Woodard C.2009. Profiling the humanprotein-DNA interactome reveals ERK2as a transcriptional repressor of interferon signaling. Cell,139(3):610-622
Humpherys D, Eggan K, Akutsu H, Friedman A, Hochedlinger K, Yanagimachi R, Lander E S, Golub T R,and Jaenisch R.2002. Abnormal gene expression in cloned mice derived from embryonic stemcell and cumulus cell nuclei. Proc Natl Acad Sci U S A,99(20):12889-12894
Humpherys D, Eggan K, Akutsu H, Hochedlinger K, Rideout W M, Biniszkiewicz D, Yanagimachi R, andJaenisch R.2001. Epigenetic instability in ES cells and cloned mice. Science,293(5527):95-97
Hurst D R, Edmonds M D, Scott G K, Benz C C, Vaidya K S, and Welch D R.2009. Breast cancermetastasis suppressor1up-regulates miR-146, which suppresses breast cancer metastasis. CancerResearch,69(4):1279-1283
Hussein S M, Batada N N, Vuoristo S, Ching R W, Autio R, Narva E, Ng S, Sourour M, Hamalainen R,Olsson C, Lundin K, Mikkola M, Trokovic R, Peitz M, Brustle O, Bazett-Jones D P, Alitalo K,Lahesmaa R, Nagy A, and Otonkoski T.2011. Copy number variation and selection duringreprogramming to pluripotency. Nature,471(7336):58-62
Hwang J H, Voortman J, Giovannetti E, Steinberg S M, Leon L G, Kim Y T, Funel N, Park J K, Kim M A,Kang G H, Kim S W, Del Chiaro M, Peters G J, and Giaccone G.2010. Identification ofmicroRNA-21as a biomarker for chemoresistance and clinical outcome following adjuvanttherapy in resectable pancreatic cancer. Plos One,5(5): e10630
Hyun S H, Lee G S, Kim D Y, Kim H S, Lee S H, Kim S, Lee E S, Lim J M, Kang S K, Lee B C, andHwang W S.2003. Effect of maturation media and oocytes derived from sows or gilts on thedevelopment of cloned pig embryos. Theriogenology,59(7):1641-1649
Iager A E, Ragina N P, Ross P J, Beyhan Z, Cunniff K, Rodriguez R M, and Cibelli J B.2008. Trichostatina improves histone acetylation in bovine somatic cell nuclear transfer early embryos. Cloning andStem Cells,10(3):371-379
Ideraabdullah F Y, Vigneau S, and Bartolomei M S.2008. Genomic imprinting mechanisms in mammals.Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis,647(1-2):77-85
Inoue A, Shen L, Dai Q, He C, and Zhang Y.2011. Generation and replication-dependent dilution of5fCand5caC during mouse preimplantation development. Cell Research,21(12):1670-1676
Inoue A, and Zhang Y.2011. Replication-dependent loss of5-hydroxymethylcytosine in mousepreimplantation embryos. Science,334(6053):194
Inoue K, Kohda T, Lee J, Ogonuki N, Mochida K, Noguchi Y, Tanemura K, Kaneko-Ishino T, Ishino F, andOgura A.2002. Faithful expression of imprinted genes in cloned mice. Science,295(5553):297-297
Inoue K, Kohda T, Sugimoto M, Sado T, Ogonuki N, Matoba S, Shiura H, Ikeda R, Mochida K, Fujii T,Sawai K, Otte A P, Tian X C, Yang X, Ishino F, Abe K, and Ogura A.2010. Impeding Xistexpression from the active X chromosome improves mouse somatic cell nuclear transfer. Science,330(6003):496-499
Iqbal K, Jin S G, Pfeifer G P, and Szabo P E.2011. Reprogramming of the paternal genome uponfertilization involves genome-wide oxidation of5-methylcytosine. Proc Natl Acad Sci U S A,108(9):3642-3647
Irie N, Takada Y, Watanabe Y, Matsuzaki Y, Naruse C, Asano M, Iwakura Y, Suda T, and Matsuo K.2009.Bidirectional signaling through ephrinA2-EphA2enhances osteoclastogenesis and suppressesosteoblastogenesis. Journal of Biological Chemistry,284(21):14637-14644
Ito S, D'Alessio A C, Taranova O V, Hong K, Sowers L C, and Zhang Y.2010. Role of Tet proteins in5mCto5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature,466(7310):1129-1133
Ito S, Shen L, Dai Q, Wu S C, Collins L B, Swenberg J A, He C, and Zhang Y.2011. Tet Proteins CanConvert5-Methylcytosine to5-Formylcytosine and5-Carboxylcytosine. Science,333(6047):1300-1303
Jin W, Dodson M V, Moore S S, Basarab J A, and Guan L L.2010. Characterization of microRNAexpression in bovine adipose tissues: a potential regulatory mechanism of subcutaneous adiposetissue development. Bmc Molecular Biology,11(1):29
Jinno Y, Sengoku K, Nakao M, Tamate K, Miyamoto T, Matsuzaka T, Sutcliffe JS, Anan T, Takuma N, andNishiwaki K I Y, Ishimaru T, Ishikawa M, Niikawa N.1996. Mouse/human sequence divergencein a region with a paternal-specific methylation imprint at the human H19locus. Hum Mol Genet,5(8):1155-1161
Jones P L, Veenstra G J C, Wade P A, Vermaak D, Kass S U, Landsberger N, Strouboulis J, and Wolffe A P.1998. Methylated DNA and MeCP2recruit histone deacetylase to repress transcription. NatureGenetics,19(2):187-191
Joyce J A, Lam W K, Catchpoole D J, Jenks P, Reik W, Maher E R, and Schofield P N.1997. Imprinting ofIGF2and H19: Lack of reciprocity in sporadic Beckwith-Wiedemann syndrome. HumanMolecular Genetics,6(9):1543-1548
Jurkowski T P, Meusburger M, Phalke S, Helm M, Nellen W, Reuter G, and Jeltsch A.2008. HumanDNMT2methylates tRNA(Asp) molecules using a DNA methyltransferase-like catalyticmechanism. Rna-a Publication of the Rna Society,14(8):1663-1670
Kalantry S, Purushothaman S, Bowen R B, Starmer J, and Magnuson T.2009. Evidence of XistRNA-independent initiation of mouse imprinted X-chromosome inactivation. Nature,460(7255):647-651
Kanduri C, Pant V, Loukinov D, Pugacheva E, Qi C F, Wolffe A, Ohlsson R, and Lobanenkov V V.2000.Functional association of CTCF with the insulator upstream of the H19gene is parent oforigin-specific and methylation-sensitive. Current Biology,10(14):853-856
Kaneda A, and Feinberg A P.2005. Loss of imprinting of IGF2: a common epigenetic modifier of intestinaltumor risk. Cancer Research,65(24):11236-11240
Kanehisa M, Araki M, Goto S, Hattori M, Hirakawa M, Itoh M, Katayama T, Kawashima S, Okuda S,Tokimatsu T, and Yamanishi Y.2008. KEGG for linking genomes to life and the environment.Nucleic Acids Research,36(Database issue): D480-D484
Kang Y K, Koo D B, Park J S, Choi Y H, Chung A S, Lee K K, and Han Y M.2001. Aberrant methylationof donor genome in cloned bovine embryos. Nature Genetics,28(2):173-177
Kano M, Seki N, Kikkawa N, Fujimura L, Hoshino I, Akutsu Y, Chiyomaru T, Enokida H, Nakagawa M,and Matsubara H.2010. miR‐145, miR‐133a and miR‐133b: Tumor‐suppressive miRNAstarget FSCN1in esophageal squamous cell carcinoma. International Journal of Cancer,127(12):2804-2814
Kato Y, Tani T, Sotomaru Y, Kurokawa K, Kato J, Doguchi H, Yasue H, and Tsunoda Y.1998. Eight calvescloned from somatic cells of a single adult. Science,282(5396):2095-2098
Kato Y, Tani T, and Tsunoda Y.2000. Cloning of calves from various somatic cell types of male and femaleadult, newborn and fetal cows. Journal of Reproduction and Fertility,120(2):231-237
Katz-Jaffe M G, McCallie B R, Preis K A, Filipovits J, and Gardner D K.2009. Transcriptome analysis ofin vivo and in vitro matured bovine MII oocytes. Theriogenology,71(6):939-946
Kishigami S, Mizutani E, Ohta H, Hikichi T, Van Thuan N, Wakayama S, Bui H T, and Wakayama T.2006.Significant improvement of mouse cloning technique by treatment with trichostatin A aftersomatic nuclear transfer. Biochemical and Biophysical Research Communications,340(1):183-189
Koh K P, Yabuuchi A, Rao S, Huang Y, Cunniff K, Nardone J, Laiho A, Tahiliani M, Sommer C A,Mostoslavsky G, Lahesmaa R, Orkin S H, Rodig S J, Daley G Q, and Rao A.2011. Tet1and Tet2regulate5-hydroxymethylcytosine production and cell lineage specification in mouse embryonicstem cells. Cell Stem Cell,8(2):200-213
Krek A, Grun D, Poy M N, Wolf R, Rosenberg L, Epstein E J, MacMenamin P, da Piedade I, Gunsalus K C,Stoffel M, and Rajewsky N.2005. Combinatorial microRNA target predictions. Nature Genetics,37(5):495-500
Kubota C, Tian X C, and Yang X Z.2004. Serial bull cloning by somatic cell nuclear transfer. NatureBiotechnology,22(6):693-694
Kubota C, Yamakuchi H, Todoroki J, Mizoshita K, Tabara N, Barber M, and Yang X Z.2000. Six clonedcalves produced from adult fibroblast cells after long-term culture. Proceedings of the NationalAcademy of Sciences of the United States of America,97(3):990-995
Lan F, and Shi Y.2009. Epigenetic regulation: methylation of histone and non-histone proteins. Science inChina Series C: Life Sciences,52(4):311-322
Lan J, Hua S, He X N, and Zhang Y.2010. DNA methyltransferases and methyl-binding proteins ofmammals. Acta Biochimica Et Biophysica Sinica,42(4):243-252
Lee B C, Kim M K, Jang G, Oh H J, Yuda F, Kim H J, Shamim M H, Kim J J, Kang S K, Schatten G, andHwang W S.2005. Dogs cloned from adult somatic cells. Nature,436(7051):641-641
Lee D Y, Hayes J J, Pruss D, and Wolffe A P.1993a. A Positive Role for Histone Acetylation inTranscription Factor Access to Nucleosomal DNA. Cell,72(1):73-84
Lee E, Estrada J, and Piedrahita J A.2008. A comparative study on the efficiency of two enucleationmethods in pig somatic cell nuclear transfer: Effects of the squeezing and the aspiration methods.Animal Biotechnology,19(2):71-79
Lee J H, and Campbell K H S.2006. Effects of enucleation and caffeine on maturation-promoting factor(MPF) and mitogen-activated protein kinase (MAPK) activities in ovine oocytes used as recipientcytoplasts for nuclear transfer. Biology of Reproduction,74(4):691-698
Lee R C, Feinbaum R L, and Ambros V.1993b. The C. elegans heterochronic gene lin-4encodes smallRNAs with antisense complementarity to lin-14. Cell,75(5):843-854
Lehnertz B, Ueda Y, Derijck A A H A, Braunschweig U, Perez-Burgos L, Kubicek S, Chen T, Li E,Jenuwein T, and Peters A H F M.2003. Suv39h-Mediated Histone H3Lysine9MethylationDirects DNA Methylation to Major Satellite Repeats at Pericentric Heterochromatin. CurrentBiology,13(14):1192-1200
Lewis B P, Burge C B, and Bartel D P.2005. Conserved seed pairing, often flanked by adenosines,indicates that thousands of human genes are microRNA targets. Cell,120(1):15-20
Li E.2002. Chromatin modification and epigenetic reprogramming in mammalian development. NatureReviews Genetics,3(9):662-673
Li E, Beard C, and Jaenisch R.1993. Role for DNA Methylation in Genomic Imprinting. Nature,366(6453):362-365
Li J, Svarcova O, Villemoes K, Kragh P M, Schmidt M, Bogh I B, Zhang Y, Du Y, Lin L, Purup S, Xue Q,Bolund L, Yang H, Maddox-Hyttel P, and Vajta G.2008a. High in vitro development after somaticcell nuclear transfer and trichostatin A treatment of reconstructed porcine embryos.Theriogenology,70(5):800-808
Li L C, and Dahiya R.2002. MethPrimer: designing primers for methylation PCRs. Bioinformatics,18(11):1427-1431
Li N, Ye M, Li Y, Yan Z, Butcher L M, Sun J, Han X, Chen Q, Zhang X, and Wang J.2010. Whole genomeDNA methylation analysis based on high throughput sequencing technology. Methods,52(3):203-212
Li Q, Li N, Hu X, Li J, Du Z, Chen L, Yin G, Duan J, Zhang H, and Zhao Y.2011. Genome-wide mappingof DNA methylation in chicken. Plos One,6(5): e19428
Li R, Yu C, Li Y, Lam T W, Yiu S M, Kristiansen K, and Wang J.2009a. SOAP2: an improved ultrafasttool for short read alignment. Bioinformatics,25(15):1966-1967
Li S J, Li Y X, Du W H, Zhang L, Yu S Y, Dai Y P, Zhao C J, and Li N.2005. Aberrant gene expression inorgans of bovine clones that die within two days after birth. Biology of Reproduction,72(2):258-265
Li X, Wang X, He K, Ma Y, Su N, He H, Stolc V, Tongprasit W, Jin W, and Jiang J.2008b. High-resolutionmapping of epigenetic modifications of the rice genome uncovers interplay between DNAmethylation, histone methylation, and gene expression. The Plant Cell Online,20(2):259-276
Li X, Yan P, and Shao Z.2009b. Downregulation of miR-193b contributes to enhance urokinase-typeplasminogen activator (uPA) expression and tumor progression and invasion in human breastcancer. Oncogene,28(44):3937-3948
Li Y, and Sasaki H.2011. Genomic imprinting in mammals: its life cycle, molecular mechanisms andreprogramming. Cell Research,21(3):466-473
Li Z Y, Sun X S, Chen J, Liu X M, Wisely S M, Zhou Q, Renard J P, Leno G H, and Engelhardt J F.2006.Cloned ferrets produced by somatic cell nuclear transfer. Developmental Biology,293(2):439-448
Lim L P, Lau N C, Garrett-Engele P, Grimson A, Schelter J M, Castle J, Bartel D P, Linsley P S, andJohnson J M.2005. Microarray analysis shows that some microRNAs downregulate largenumbers of target mRNAs. Nature,433(7027):769-773
Lin L, Li Q, Zhang L, Zhao D S, Dai Y P, and Li N.2008. Aberrant epigenetic changes and geneexpression in cloned cattle dying around birth. Bmc Developmental Biology,8(14):1-10
Lister R, Pelizzola M, Dowen R H, Hawkins R D, Hon G, Tonti-Filippini J, Nery J R, Lee L, Ye Z, Ngo QM, Edsall L, Antosiewicz-Bourget J, Stewart R, Ruotti V, Millar A H, Thomson J A, Ren B, andEcker J R.2009. Human DNA methylomes at base resolution show widespread epigenomicdifferences. Nature,462(7271):315-322
Lister R, Pelizzola M, Kida Y S, Hawkins R D, Nery J R, Hon G, Antosiewicz-Bourget J, O'Malley R,Castanon R, Klugman S, Downes M, Yu R, Stewart R, Ren B, Thomson J A, Evans R M, andEcker J R.2011. Hotspots of aberrant epigenomic reprogramming in human induced pluripotentstem cells. Nature,471(7336):68-84
Liu F J, Zhang Y, Zheng Y M, Zhao M T, Zhang Y L, Wang Y S, Wang G H, Quan F S, and An Z X.2007.Optimization of electrofusion protocols for somatic cell nuclear transfer. Small Ruminant Research,73(1-3):246-251
Liu J H, Yin S, Xiong B, Hou Y, Chen D Y, and Sun Q Y.2008. Aberrant DNA methylation imprints inaborted bovine clones. Molecular Reproduction and Development,75(4):598-607
Liu N, Enkemann S A, Liang P, Hersmus R, Zanazzi C, Huang J, Wu C, Chen Z, Looijenga L H J, andKeefe D L.2010. Genome-wide gene expression profiling reveals aberrant MAPK and Wntsignaling pathways associated with early parthenogenesis. Journal of molecular cell biology,2(6):333-344
Loenarz C, and Schofield C J.2011. Physiological and biochemical aspects of hydroxylations anddemethylations catalyzed by human2-oxoglutarate oxygenases. Trends in Biochemical Sciences,36(1):7-18
Loi P, Ledda S, Fulka J, Jr., Cappai P, and Moor R M.1998. Development of parthenogenetic and clonedovine embryos: effect of activation protocols. Biology of Reproduction,58(5):1177-1187
Lonergan P, Monaghan P, Rizos D, Boland M P, and Gordon I.1994. Effect of follicle size on bovineoocyte quality and developmental competence following maturation, fertilization, and culture invitro. Molecular Reproduction and Development,37(1):48-53
Long J E, and Cai X.2007. Igf-2r expression regulated by epigenetic modification and the locus of geneimprinting disrupted in cloned cattle. Gene,388(1-2):125-134
Long J E, Cai X, and He L Q.2007. Gene profiling of cattle blastocysts derived from nuclear transfer, invitro fertilization and in vivo development based on cDNA library. Animal Reproduction Science,100(3-4):243-256
Lorsbach R, Moore J, Mathew S, Raimondi S, Mukatira S, and Downing J.2003. TET1, a member of anovel protein family, is fused to MLL in acute myeloid leukemia containing the t(10;11)(q22;q23). Leukemia,17(3):637-641
Lucifero D, Mertineit C, Clarke H J, Bestor T H, and Trasler J M.2002. Methylation dynamics ofimprinted genes in mouse germ cells. Genomics,79(4):530-538
Lucifero D, Suzuki J, Bordignon V, Martel J, Vigneault C, Therrien J, Filion F, Smith L C, and Trasler J M.2006. Bovine SNRPN methylation imprint in oocytes and day17in vitro-produced and somaticcell nuclear transfer embryos. Biology of Reproduction,75(4):531-538
Ma L, Reinhardt F, Pan E, Soutschek J, Bhat B, Marcusson E G, Teruya-Feldstein J, Bell G W, andWeinberg R A.2010. Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammarytumor model. Nature Biotechnology,28(4):341-347
Ma L, Teruya-Feldstein J, and Weinberg R A.2007. Tumour invasion and metastasis initiated bymicroRNA-10b in breast cancer. Nature,449(7163):682-688
Ma S F, Liu X Y, Miao D Q, Han Z B, Zhang X, Miao Y L, Yanagimachi R, and Tan J H.2005.Parthenogenetic activation of mouse oocytes by strontium chloride: a search for the bestconditions. Theriogenology,64(5):1142-1157
Maalouf W E, Liu Z C, Brochard V, Renard J P, Debey P, Beaujean N, and Zink D.2009. Trichostatin Atreatment of cloned mouse embryos improves constitutive heterochromatin remodeling as well asdevelopmental potential to term. Bmc Developmental Biology,9(11):1-6
Maatouk D M, and Resnick J L.2003. Continuing primordial germ cell differentiation in the mouseembryo is a cell-intrinsic program sensitive to DNA methylation. Developmental Biology,258(1):201-208
Maiti A, and Drohat A C.2011. Thymine DNA glycosylase can rapidly excise5-formylcytosine and5-carboxylcytosine: Potential implications for active demethylation of CpG sites. Journal ofBiological Chemistry,286(41):35334-3538
Mallory A C, and Vaucheret H.2006. Functions of microRNAs and related small RNAs in plants. NatureGenetics,38Suppl: S31-S36
Mann M R W, Chung Y G, Nolen L D, Verona R I, Latham K E, and Bartolomei M S.2003. Disruption ofimprinted gene methylation and expression in cloned preimplantation stage mouse embryos.Biology of Reproduction,69(3):902-914
Masui S, Nakatake Y, Toyooka Y, Shimosato D, Yagi R, Takahashi K, Okochi H, Okuda A, Matoba R,Sharov A A, Ko M S H, and Niwa H.2007. Pluripotency governed by Sox2via regulation ofOct3/4expression in mouse embryonic stem cells. Nature Cell Biology,9(6):625-626
Matoba S, Inoue K, Kohda T, Sugimoto M, Mizutani E, Ogonuki N, Nakamura T, Abe K, Nakano T, IshinoF, and Ogura A.2011. RNAi-mediated knockdown of Xist can rescue the impairedpostimplantation development of cloned mouse embryos. Proc Natl Acad Sci U S A,108(51):20621-20626
Md H, Nasser G, Michael H, Franca R, Chirawath P, Ernst T, Karl S, and Dawit T.2009. Identification andcharacterization of miRNAs expressed in the bovine ovary. Bmc Genomics,10:443
Meissner A, Mikkelsen T S, Gu H, Wernig M, Hanna J, Sivachenko A, Zhang X, Bernstein B E, NusbaumC, and Jaffe D B.2008. Genome-scale DNA methylation maps of pluripotent and differentiatedcells. Nature,454(7205):766-770
Meng F, Henson R, Lang M, Wehbe H, Maheshwari S, Mendell J T, Jiang J, Schmittgen T D, and Patel T.2006. Involvement of human micro-RNA in growth and response to chemotherapy in humancholangiocarcinoma cell lines. Gastroenterology,130(7):2113-2129
Meng Q G, Polgar Z, Liu J, and Dinnyes A.2009. Live Birth of Somatic Cell-Cloned Rabbits followingTrichostatin A Treatment and Cotransfer of Parthenogenetic Embryos. Cloning and Stem Cells,11(1):203-208
Mendez M G, Kojima S I, and Goldman R D.2010. Vimentin induces changes in cell shape, motility, andadhesion during the epithelial to mesenchymal transition. The FASEB Journal,24(6):1838-1851
Miglino M A, Pereira F T V, Visintin J A, Garcia J M, Meirelles F V, Rumpf R, Ambrosio C E, Papa P C,Santos T C, Carvalho A F, Leiser R, and Carter A M.2007. Placentation in cloned cattle: Structureand microvascular architecture. Theriogenology,68(4):604-617
Mikkelsen T S, Ku M, Jaffe D B, Issac B, Lieberman E, Giannoukos G, Alvarez P, Brockman W, Kim T K,and Koche R P.2007. Genome-wide maps of chromatin state in pluripotent and lineage-committedcells. Nature,448(7153):553-560
Miles J R, McDaneld T G, Wiedmann R T, Cushman R A, Echternkamp S E, Vallet J L, and Smith T P.2012. MicroRNA expression profile in bovine cumulus-oocyte complexes: possible role of let-7and miR-106a in the development of bovine oocytes. Animal Reproduction Science,130(1-2):16-26
Misri S, Pandita S, Kumar R, and Pandita T.2008. Telomeres, histone code, and DNA damage response.Cytogenetic and Genome Research,122(3-4):297-307
Miyoshi K, Mori H, Mizobe Y, Akasaka E, Ozawa A, Yoshida M, and Sato M.2010. Valproic acidenhances in vitro development and Oct-3/4expression of miniature pig somatic cell nucleartransfer embryos. Cellular Reprogramming,12(1):67-74
Miyoshi K, Rzucidlo S J, Pratt S L, and Stice S L.2003. Improvements in cloning efficiencies may bepossible by increasing uniformity in recipient oocytes and donor cells. Biology of Reproduction,68(4):1079-1086
Mortazavi A, Williams B A, McCue K, Schaeffer L, and Wold B.2008. Mapping and quantifyingmammalian transcriptomes by RNA-Seq. Nature Methods,5(7):621-628
Murrell A, Heeson S, and Reik W.2004. Interaction between differentially methylated regions partitionsthe imprinted genes Igf2and H19into parent-specific chromatin loops. Nature Genetics,36(8):889-893
Nagayoshi S, Hayashi E, Abe G, Osato N, Asakawa K, Urasaki A, Horikawa K, Ikeo K, Takeda H, andKawakami K.2008. Insertional mutagenesis by the Tol2transposon-mediated enhancer trapapproach generated mutations in two developmental genes: tcf7and synembryn-like. Development,135(1):159-169
Nahid M A, Pauley K M, Satoh M, and Chan E K L.2009. miR-146a Is Critical for Endotoxin-inducedTolerance. Journal of Biological Chemistry,284(50):34590-34599
Nan X, Ng H H, Johnson C A, Laherty C D, Turner B M, Eisenman R N, and Bird A.1998. Transcriptionalrepression by the methyl-CpG-binding protein MeCP2involves a histone deacetylase complex.Nature,393(6683):386-389
Niwa H, Toyooka Y, Shimosato D, Strumpf D, Takahashi K, Yagi R, and Rossant J.2005. Interactionbetween Oct3/4and Cdx2determines trophectoderm differentiation. Cell,123(5):917-930
Ng S, Yue W, Oppermann U, and Klose R.2009. Dynamic protein methylation in chromatin biology.Cellular and Molecular Life Sciences,66(3):407-422
Noble J A, White A M, Lazzeroni L C, Valdes A M, Mirel D B, Reynolds R, Grupe A, Aud D, Peltz G, andErlich H A.2003. A polymorphism in the TCF7gene, C883A, is associated with type1diabetes.Diabetes,52(6):1579-1582
Noonan E.2009. miR-449a targets HDAC-1and induces growth arrest in prostate cancer. Oncogene,28(14):1714-1724
Noonan E J.2010. miR-449a causes Rb-dependent cell cycle arrest and senescence in prostate cancer cells.Oncotarget,1(5):349-358
Norris D P, Patel D, Kay G F, Penny G D, Brockdorff N, Sheardown S A, and Rastan S.1994. Evidencethat random and imprinted Xist expression is controlled by preemptive methylation. Cell,77(1):41-51
Nowak S J, and Corces V G.2004. Phosphorylation of histone H3: a balancing act between chromosomecondensation and transcriptional activation. Trends in Genetics,20(4):214-220
Oback B, and Wells D N.2003. Cloning cattle. Cloning and Stem Cells,5(4):243-256
Ogawa H, Ono Y, Shimozawa N, Sotomaru Y, Katsuzawa Y, Hiura H, Ito M, and Kono T.2003. Disruptionof imprinting in cloned mouse fetuses from embryonic stem cells. Reproduction,126(4):549-557
Ogonuki N, Inoue K, Yamamoto Y, Noguchi Y, Tanemura K, Suzuki O, Nakayama H, Doi K, Ohtomo Y,Satoh M, Nishida A, and Ogura A.2002. Early death of mice cloned from somatic cells. NatureGenetics,30(3):253-254
Ogura A, Inoue K, Ogonuki N, Noguchi A, Takano K, Nagano R, Suzuki O, Lee J, Ishino F, and Matsuda J.2000. Production of male cloned mice from fresh, cultured, and cryopreserved immature Sertolicells. Biology of Reproduction,62(6):1579-1584
Okamoto I, Patrat C, Thepot D, Peynot N, Fauque P, Daniel N, Diabangouaya P, Wolf J P, Renard J P,Duranthon V, and Heard E.2011. Eutherian mammals use diverse strategies to initiateX-chromosome inactivation during development. Nature,472(7343):370-374
Oki M, Aihara H, and Ito T.2007. Role of histone phosphorylation in chromatin dynamics and itsimplications in diseases. Chromatin and Disease,41:323-340
Onishi A, Iwamoto M, Akita T, Mikawa S, Takeda K, Awata T, Hanada H, and Perry A C F.2000. Pigcloning by microinjection of fetal fibroblast nuclei. Science,289(5482):1188-1190
Ono R, Taki T, Taketani T, Taniwaki M, Kobayashi H, and Hayashi Y.2002. LCX, leukemia-associatedprotein with a CXXC domain, is fused to MLL in acute myeloid leukemia with trilineagedysplasia having t(10;11)(q22;q23). Cancer Research,62(14):4075-4080
Ono T, Li C, Mizutani E, Terashita Y, Yamagata K, and Wakayama T.2010. Inhibition of Class IIb HistoneDeacetylase Significantly Improves Cloning Efficiency in Mice. Biology of Reproduction,83(6):929-937
Pérez-Cadahía B P C B, Drobic B D B, and Davie J R D J R.2009. H3phosphorylation: dual role inmitosis and interphase This paper is one of a selection of papers published in this Special Issueentitled30th Annual International Asilomar Chromatin and Chromosomes Conference and hasundergone the Journal's usual peer review process. Biochemistry and Cell Biology,87(5):695-709
Park J Y, Park M R, Hwang K C, Chung J S, Bui H T, Kim T, Cho S K, Kim J H, Hwang S, Park S B, andNguyen V T.2011. Comparative gene expression analysis of somatic cell nuclear transfer-derivedcloned pigs with normal and abnormal umbilical cords. Biology of Reproduction,84(1):189-99
Parthun M.2007. Hat1: the emerging cellular roles of a type B histone acetyltransferase. Oncogene,26(37):5319-5328
Pase L, Layton J E, Kloosterman W P, Carradice D, Waterhouse P M, and Lieschke G J.2009. miR-451regulates zebrafish erythroid maturation in vivo via its target gata2. Blood,113(8):1794-1804
Pastor W A, Pape U J, Huang Y, Henderson H R, Lister R, Ko M, McLoughlin E M, Brudno Y, MahapatraS, Kapranov P, Tahiliani M, Daley G Q, Liu X S, Ecker J R, Milos P M, Agarwal S, and Rao A.2011. Genome-wide mapping of5-hydroxymethylcytosine in embryonic stem cells. Nature,473(7347):394-397
Penn N, Suwalski R, O'Riley C, Bojanowski K, and Yura R.1972. The presence of5-hydroxymethylcytosine in animal deoxyribonucleic acid. Biochemical Journal,126(4):781-790
Pfaffeneder T, Hackner B, Tru M, Münzel M, Müller M, Deiml C A, Hagemeier C, and Carell T.2011.The Discovery of5‐Formylcytosine in Embryonic Stem Cell DNA.Angewandte Chemie,123(31):7146-7150
Pinter S F, Sadreyev R I, Yildirim E, Jeon Y, Ohsumi T K, Borowsky M, and Lee J T.2012. Spreading of Xchromosome inactivation via a hierarchy of defined Polycomb stations. Genome Res,22(10):1864-1876
Plath K.2003. Role of histone H3lysine27methylation in X inactivation. Science,300(5616):131-135
Pokholok D K, Harbison C T, Levine S, Cole M, Hannett N M, Lee T I, Bell G W, Walker K, Rolfe P A,and Herbolsheimer E.2005. Genome-wide map of nucleosome acetylation and methylation inyeast. Cell,122(4):517-527
Popp C, Dean W, Feng S, Cokus S J, Andrews S, Pellegrini M, Jacobsen S E, and Reik W.2010.Genome-wide erasure of DNA methylation in mouse primordial germ cells is affected by AIDdeficiency. Nature,463(7284):1101-1105
Powell A M, Talbot N C, Wells K D, Kerr D E, Pursel V G, and Wall R J.2004. Cell donor influencessuccess of producing cattle by somatic cell nuclear transfer. Biology of Reproduction,71(1):210-216
Pujol M, Lopez-Bejar M, and Paramio M T.2004. Developmental competence of heifer oocytes selectedusing the brilliant cresyl blue (BCB) test. Theriogenology,61(4):735-744
Reik W, Bowden L, Constancia M, Dean W, Feil R, Forne T, Kelsey G, Maher E, Moore T, Sun F L, andWalter J.1996. Regulation of Igf2imprinting in development and disease. International Journalof Developmental Biology, Suppl1:53S-54S
Reik W, Brown K W, Schneid H, Le Bouc Y, Bickmore W, and Maher E R.1995. Imprinting mutations inthe Beckwith—Wiedemann syndrome suggested by an altered imprinting pattern in the IGF2–H19domain. Human Molecular Genetics,4(12):2379-2385
Renard J P, Chastant S, Chesne P, Richard C, Marchal J, Cordonnier N, Chavatte P, and Vignon X.1999.Lymphoid hypoplasia and somatic cloning. Lancet,353(9163):1489-1491
Rizos D, Burke L, Duffy P, Wade M, Mee J F, O'Farrell K J, Macsiurtain M, Boland M P, and Lonergan P.2005. Comparisons between nulliparous heifers and cows as oocyte donors for embryo productionin vitro. Theriogenology,63(3):939-949
Roca J, Martinez E, Vazquez J M, and Lucas X.1998. Selection of immature pig oocytes for homologousin vitro penetration assays with the brilliant cresyl blue test. Reprod Fertil Dev,10(6):479-485
Rodrigues B A, Rodriguez P, Silva A E, Cavalcante L F, Feltrin C, and Rodrigues J L.2009. Preliminarystudy in immature canine oocytes stained with brilliant cresyl blue and obtained from bitches withlow and high progesterone serum profiles. Reproduction in Domestic Animals,44Suppl2:255-258
Rodriguez-Gonzalez E, Lopez-Bejar M, Izquierdo D, and Paramio M T.2003. Developmental competenceof prepubertal goat oocytes selected with brilliant cresyl blue and matured with cysteaminesupplementation. Reproduction Nutrition Development,43(2):179-187
Rodriguez-Gonzalez E, Lopez-Bejar M, Velilla E, and Paramio M T.2002. Selection of prepubertal goatoocytes using the brilliant cresyl blue test. Theriogenology,57(5):1397-409
Ruike Y, Imanaka Y, Sato F, Shimizu K, and Tsujimoto G.2010. Genome-wide analysis of aberrantmethylation in human breast cancer cells using methyl-DNA immunoprecipitation combined withhigh-throughput sequencing. Bmc Genomics,11:137
Rybouchkin A, Kato Y, and Tsunodaz Y.2006. Role of histone acetylation in reprogramming of somaticnuclei following nuclear transfer. Biology of Reproduction,74(6):1083-1089
Sado T, and Brockdorff N.2013. Advances in understanding chromosome silencing by the longnon-coding RNA Xist. Philos Trans R Soc Lond B Biol Sci,368(1609):20110325
Sartori R, Sartor-Bergfelt R, Mertens S A, Guenther J N, Parrish J J, and Wiltbank M C.2002. Fertilizationand early embryonic development in heifers and lactating cows in summer and lactating and drycows in winter. Journal of Dairy Science,85(11):2803-2812
Sato N, Meijer L, Skaltsounis L, Greengard P, and Brivanlou A H.2004. Maintenance of pluripotency inhuman and mouse embryonic stem cells through activation of Wnt signaling by a pharmacologicalGSK-3-specific inhibitor. Nature Medicine,10(1):55-63
Schaar C, Kluin-Nelemans H, Te Marvelde C, Le Cessie S, Breed W, Fibbe W, Van Deijk W, Fickers M,Roozendaal K, and Wijermans P.2005. Interferon-α as maintenance therapy in patients withmultiple myeloma. Annals of Oncology,16(4):634-639
Shao G B, Ding H M, and Gong A H.2008a. Role of histone methylation in zygotic genome activation inthe preimplantation mouse embryo. In Vitro Cell Dev Biol Anim,44(3-4):115-120
Shao G B, Ding H M, Gong A H, and Xiao D S.2008b. Inheritance of histone H3methylation inreprogramming of somatic nuclei following nuclear transfer. J Reprod Dev,54(3):233-238
Sharif J, Muto M, Takebayashi S, Suetake I, Iwamatsu A, Endo T A, Shinga J, Mizutani-Koseki Y, ToyodaT, Okamura K, Tajima S, Mitsuya K, Okano M, and Koseki H.2007. The SRA protein Np95mediates epigenetic inheritance by recruiting Dnmt1to methylated DNA. Nature,450(7171):908-912
Shen C J, Cheng W T K, Wu S C, Chen H L, Tsai T C, Yang S H, and Chen C M.2012. DifferentialDifferences in Methylation Status of Putative Imprinted Genes among Cloned Swine Genomes.Plos One,7(2): e32812
Shen L, Kondo Y, Guo Y, Zhang J, Zhang L, Ahmed S, Shu J, Chen X, Waterland R A, and Issa J P J.2007.Genome-wide profiling of DNA methylation reveals a class of normally methylated CpG islandpromoters. Plos Genetics,3(10): e181
Shi L H, Miao Y L, Ouyang Y C, Huang J C, Lei Z L, Yang J W, Han Z M, Song X F, Sun Q Y, and ChenD Y.2008. Trichostatin a (TSA) improves the development of rabbit-rabbit intraspecies clonedembryos, but not rabbit-human interspecies cloned embryos. Developmental Dynamics,237(3):640-648
Shi W, Hoeflich A, Flaswinkel H, Stojkovic M, Wolf E, and Zakhartchenko V.2003. Induction of asenescent-like phenotype does not confer the ability of bovine immortal cells to support thedevelopment of nuclear transfer embryos. Biology of Reproduction,69(1):301-309
Shin T, Kraemer D, Pryor J, Liu L, Rugila J, Howe L, Buck S, Murphy K, Lyons L, and Westhusin M.2002. A cat cloned by nuclear transplantation. Nature,415(6874):859-859
Sibley C P, Coan P M, Ferguson-Smith A C, Dean W, Hughes J, Smith P, Reik W, Burton G J, Fowden A L,and Constancia M.2004. Placental-specific insulin-like growth factor2(Igf2) regulates thediffusional exchange characteristics of the mouse placenta. Proceedings of the National Academyof Sciences of the United States of America,101(21):8204-8208
Sleutels F, Zwart R, and Barlow D P.2002. The non-coding Air RNA is required for silencing autosomalimprinted genes. Nature,415(6873):810-813
Smallwood A, Estève P O, Pradhan S, and Carey M.2007. Functional cooperation between HP1andDNMT1mediates gene silencing. Genes&Development,21(10):1169-1178
Smith S L, Everts R E, Tian X C, Du F, Sung L Y, Rodriguez-Zas S L, Jeong B S, Renard J P, Lewin H A,and Yang X.2005. Global gene expression profiles reveal significant nuclear reprogramming bythe blastocyst stage after cloning. Proc Natl Acad Sci U S A,102(49):17582-1757
Stec I, Nagl S B, van Ommen G J, and den Dunnen J T.2000. The PWWP domain: a potentialprotein-protein interaction domain in nuclear proteins influencing differentiation? Febs Letters,473(1):1-5
Stock A E, and Fortune J E.1993. Ovarian Follicular Dominance in Cattle-Relationship betweenProlonged Growth of the Ovulatory Follicle and Endocrine Parameters. Endocrinology,132(3):1108-1114
Su J M, Wang Y S, Liu Q, Yang B, Wu Y Y, Luo Y, Hu G D, and Zhang Y.2011a. Aberrant mRNAexpression and DNA methylation levels of imprinted genes in cloned transgenic calves that died oflarge offspring syndrome. Livestock Science,141(1):24-35
Su J M, Yang B, Wang Y S, Li Y Y, Xiong X R, Wang L J, Guo Z K, and Zhang Y.2011b. Expression andmethylation status of imprinted genes in placentas of deceased and live cloned transgenic calves.Theriogenology,75(7):1346-1359
Su J, Wang Y, Li Y, Li R, Li Q, Wu Y, Quan F, Liu J, Guo Z, and Zhang Y.2011c. Oxamflatin significantlyimproves nuclear reprogramming, blastocyst quality, and in vitro development of bovine SCNTembryos. Plos One,6(8): e23805
Suemizu H, Aiba K, Yoshikawa T, Sharov A A, Shimozawa N, Tamaoki N, and Ko M S.2003. Expressionprofiling of placentomegaly associated with nuclear transplantation of mouse ES cells.Developmental Biology,253(1):36-53
Sun F L, Dean W L, Kelsey G, Allen N D, and Reik W.1997. Transactivation of Igf2in a mouse model ofBeckwith-Wiedemann syndrome. Nature,389(6653):809-815
Suzuki J, Jr., Therrien J, Filion F, Lefebvre R, Goff A K, Perecin F, Meirelles F V, and Smith L C.2011.Loss of methylation at H19DMD is associated with biallelic expression and reduced developmentin cattle derived by somatic cell nuclear transfer. Biology of Reproduction,84(5):947-956
Suzuki Jr J, Therrien J, Filion F, Lefebvre R, Goff A, Perecin F, Meirelles F, and Smith L.2011. Loss ofmethylation at H19DMD is associated with biallelic expression and reduced development in cattlederived by somatic cell nuclear transfer. Biology of Reproduction,84(5):947-956
Taganov K D, Boldin M P, Chang K J, and Baltimore D.2006. NF-κB-dependent induction of microRNAmiR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proceedings ofthe National Academy of Sciences,103(33):12481-12486
Tahara E, Tahara H, Kanno M, Naka K, Takeda Y, Matsuzaki T, Yamazaki R, Ishihara H, Yasui W, andBarrett J C.2005. G1P3, an interferon inducible gene6-16, is expressed in gastric cancers andinhibits mitochondrial-mediated apoptosis in gastric cancer cell line TMK-1cell. CancerImmunology, Immunotherapy,54(8):729-740
Tahiliani M, Koh K P, Shen Y, Pastor W A, Bandukwala H, Brudno Y, Agarwal S, Iyer L M, Liu D R,Aravind L, and Rao A.2009. Conversion of5-methylcytosine to5-hydroxymethylcytosine inmammalian DNA by MLL partner TET1. Science,324(5929):930-935
Tao H, Suzuki M, Kiyonari H, Abe T, Sasaoka T, and Ueno N.2009. Mouse prickle1, the homolog of aPCP gene, is essential for epiblast apical-basal polarity. Proceedings of the National Academy ofSciences,106(34):14426-14431
Thomson J P, Skene P J, Selfridge J, Clouaire T, Guy J, Webb S, Kerr A R, Deaton A, Andrews R, James KD, Turner D J, Illingworth R, and Bird A.2010. CpG islands influence chromatin structure via theCpG-binding protein Cfp1. Nature,464(7291):1082-1086
Thorvaldsen J L, Duran K L, and Bartolomei M S.1998. Deletion of the H19differentially methylateddomain results in loss of imprinted expression of H19and Igf2. Genes&Development,12(23):3693-3702
Tian X C, Kubota C, Enright B, and Yang X.2003. Cloning animals by somatic cell nucleartransfer--biological factors. Reprod Biol Endocrinol,1:98
Tian X C, Xu J, and Yang X Z.2000. Normal telomere lengths found in cloned cattle. Nature Genetics,26(3):272-273
Torner H, Ghanem N, Ambros C, Holker M, Tomek W, Phatsara C, Alm H, Sirard M A, Kanitz W,Schellander K, and Tesfaye D.2008. Molecular and subcellular characterisation of oocytesscreened for their developmental competence based on glucose-6-phosphate dehydrogenaseactivity. Reproduction,135(2):197-212
Tremblay K D, Duran K L, and Bartolomei M S.1997. A5'2-kilobase-pair region of the imprinted mouseH19gene exhibits exclusive paternal methylation throughout development. Molecular andCellular Biology,17(8):4322-4329
Urabe A.1994. Interferons for the treatment of hematological malignancies. Oncology,51(2):137-141
Valinluck V, and Sowers L C.2007. Endogenous cytosine damage products alter the site selectivity ofhuman DNA maintenance methyltransferase DNMT1. Cancer Research,67(3):946-950
Van Thuan N, Bui H T, Kim J H, Hikichi T, Wakayama S, Kishigami S, Mizutani E, and Wakayama T.2009. The histone deacetylase inhibitor scriptaid enhances nascent mRNA production and rescuesfull-term development in cloned inbred mice. Reproduction,138(2):309-317
Vassena R, Han Z, Gao S, Baldwin D A, Schultz R M, and Latham K E.2007. Tough beginnings:alterations in the transcriptome of cloned embryos during the first two cell cycles. DevelopmentalBiology,304(1):75-89
Vassena R, Mapletoft R J, Allodi S, Singh J, and Adams G P.2003. Morphology and developmentalcompetence of bovine oocytes relative to follicular status. Theriogenology,60(5):923-932
Vucic E A, Wilson I M, Campbell J M, and Lam W L.2009. Methylation Analysis by DNAImmunoprecipitation(MeDIP). Methods in Molecular Biology,556:141-153
Wakayama T, Perry A C F, Zuccotti M, Johnson K R, and Yanagimachi R.1998. Full-term development ofmice from enucleated oocytes injected with cumulus cell nuclei. Nature,394(6691):369-374
Wakayama T, and Yanagimachi R.2001. Mouse cloning with nucleus donor cells of different age and type.Molecular Reproduction and Development,58(4):376-383
Wang L J, Zhang H, Wang Y S, Xu W B, Xiong X R, Li Y Y, Su J M, Hua S, and Zhang Y.2011a. ScriptaidImproves In Vitro Development and Nuclear Reprogramming of Somatic Cell Nuclear TransferBovine Embryos. Cellular Reprogramming,13(5):431-439
Wang S, Aurora A B, Johnson B A, Qi X, McAnally J, Hill J A, Richardson J A, Bassel-Duby R, and OlsonE N.2008. The endothelial-specific microRNA miR-126governs vascular integrity andangiogenesis. Developmental Cell,15(2):261-271
Wang Y, Medvid R, Melton C, Jaenisch R, and Blelloch R.2007. DGCR8is essential for microRNAbiogenesis and silencing of embryonic stem cell self-renewal. Nature Genetics,39(3):380-385
Wang Y, Liu J, Tang S, An Z, Guo Z, Ding X, Liu F, Cao Z, Zhang T, and Zhang Y.2009. Modifications ofchemically induced-enucleated nuclear transfer technique by reverse-order nuclear transfer inmouse. Zygote,17(3):261-268
Wang Y, Su J, Wang L, Xu W, Quan F, Liu J, and Zhang Y.2011b. The Effects of5-Aza-2'-Deoxycytidineand Trichostatin A on Gene Expression and DNA Methylation status in Cloned Bovine Blastocysts.Cellular Reprogramming,13(4):297-306
Wang Y S, Tang S, An Z X, Li W Z, Liu J, Quan F S, Hua S, and Zhang Y.2011c. Effect of mSOF andG1.1/G2.2Media on the Developmental Competence of SCNT-Derived Bovine Embryos.Reproduction in Domestic Animals,46(3):404-409
Wang Y S, Xiong X R, An Z X, Wang L J, Liu J, Quan F S, Hua S, and Zhang Y.2011d. Production ofcloned calves by combination treatment of both donor cells and early cloned embryos with5-aza-2′-deoxycytidine and trichostatin A. Theriogenology,75(5):819–825
Wang Y S, Zhao X, Su J M, An Z X, Xiong X R, Wang L J, Liu J, Quan F S, Hua S, and Zhang Y.2011e.Lowering storage temperature during ovary transport is beneficial to the developmentalcompetence of bovine oocytes used for somatic cell nuclear transfer. Animal Reproduction Science,124(1-2):48-54
Warzych E, Peippo J, Szydlowski M, and Lechniak D.2007. Supplements to in vitro maturation mediaaffect the production of bovine blastocysts and their apoptotic index but not the proportions ofmatured and apoptotic oocytes. Animal Reproduction Science,97(3-4):334-343
Weber M, Davies J J, Wittig D, Oakeley E J, Haase M, Lam W L, and Schübeler D.2005.Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylationin normal and transformed human cells. Nature Genetics,37(8):853-862
Weber M, Hellmann I, Stadler M B, Ramos L, P bo S, Rebhan M, and Schübeler D.2007. Distribution,silencing potential and evolutionary impact of promoter DNA methylation in the human genome.Nature Genetics,39(4):457-466
Wee G, Shim J J, Koo D B, Chae J I, Lee K K, and Han Y M.2007. Epigenetic alteration of the donor cellsdoes not recapitulate the reprogramming of DNA methylation in cloned embryos. Reproduction,134(6):781-787
Wei Y C, Zhu J, Huan Y J, Liu Z F, Yang C R, Zhang X M, Mu Y S, Xia P, and Liu Z H.2010. AberrantExpression and Methylation Status of Putatively Imprinted Genes in Placenta of Cloned Piglets.Cellular Reprogramming,12(2):213-222
Wightman B, Ha I, and Ruvkun G.1993. Posttranscriptional regulation of the heterochronic gene lin-14bylin-4mediates temporal pattern formation in C. elegans. Cell,75(5):855-862
Wilmut I, Beaujean N, de Sousa P A, Dinnyes A, King T J, Paterson L A, Wells D N, and Young L E.2002.Somatic cell nuclear transfer. Nature,419(6907):583-586
Wilmut I, Schnieke A E, McWhir J, Kind A J, and Campbell K H S.1997. Viable offspring derived fromfetal and adult mammalian cell. Nature,386(6619):810-813
Willinger T, Freeman T, Herbert M, Hasegawa H, McMichael A J, and Callan M F C.2006. Human naiveCD8T cells down-regulate expression of the WNT pathway transcription factors lymphoidenhancer binding factor1and transcription factor7(T cell factor-1) following antigen encounterin vitro and in vivo. The Journal of Immunology,176(3):1439-1446
Woods G L, White K L, Vanderwall D K, Li G P, Aston K I, Bunch T D, Meerdo L N, and Pate B J.2003.A mule cloned from fetal cells by nuclear transfer. Science,301(5636):1063-1063
Wossidlo M, Nakamura T, Lepikhov K, Marques C J, Zakhartchenko V, Boiani M, Arand J, Nakano T,Reik W, and Walter J.2011.5-Hydroxymethylcytosine in the mammalian zygote is linked withepigenetic reprogramming. Nature Communications,2:241
Wrenzycki C, Lucas-Hahn A, Herrmann D, Lemme E, Korsawe K, and Niemann H.2002b. In vitroproduction and nuclear transfer affect dosage compensation of the X-linked gene transcripts G6PD,PGK, and Xist in preimplantation bovine embryos. Biology of Reproduction,66(1):127-134
Wu J Q, Seay M, Schulz V P, Hariharan M, Tuck D, Lian J, Du J, Shi M, Ye Z, and Gerstein M.2012. Tcf7Is an Important Regulator of the Switch of Self-Renewal and Differentiation in a MultipotentialHematopoietic Cell Line. Plos Genetics,8(3): e1002565
Wu H, and Zhang Y.2011a. Mechanisms and functions of Tet protein-mediated5-methylcytosine oxidation.Genes Dev,25(23):2436-2452
Wu H, and Zhang Y.2011b. Tet1and5-hydroxymethylation: A genome-wide view in mouse embryonicstem cells. Cell Cycle,10(15):2428-2436
Wu S C, and Zhang Y.2010. Active DNA demethylation: many roads lead to Rome. Nat Rev Mol Cell Biol,11(9):607-620
Wu Y G, Liu Y, Zhou P, Lan G C, Han D, Miao D Q, and Tan J H.2007. Selection of oocytes for in vitromaturation by brilliant cresyl blue staining: a study using the mouse model. Cell Research,17(8):722-731
Xia H, Qi Y, Ng S S, Chen X, Li D, Chen S, Ge R, Jiang S, Li G, and Chen Y.2009. microRNA-146binhibits glioma cell migration and invasion by targeting MMPs. Brain Research,1269:158-165
Xu W, Yang H, Liu Y, Yang Y, Wang P, Kim S H, Ito S, Yang C, and Xiao M T.2011. Oncometabolite2-Hydroxyglutarate Is a Competitive Inhibitor of [alpha]-Ketoglutarate-Dependent Dioxygenases.Cancer Cell,19(1):17-30
Xue F, Tian X C, Du F, Kubota C, Taneja M, Dinnyes A, Dai Y, Levine H, Pereira L V, and Yang X.2002.Aberrant patterns of X chromosome inactivation in bovine clones. Nat Genet,31(2):216-220
Yamanaka K, Sugimura S, Wakai T, Kawahara M, and Sato E.2009. Acetylation Level of Histone H3inEarly Embryonic Stages Affects Subsequent Development of Miniature Pig Somatic Cell NuclearTransfer Embryos. Journal of Reproduction and Development,55(6):638-644
Yang C R, Miao D Q, Zhang Q H, Guo L, Tong J S, Wei Y, Huang X, Hou Y, Schatten H, Liu Z, and Sun QY.2010. Short-term preservation of porcine oocytes in ambient temperature: novel approaches.Plos One,5(12): e14242
Yang F K, Hao R, Kessler B, Brem G, Wolf E, and Zakhartchenko V.2007a. Rabbit somatic cell cloning:effects of donor cell type, histone acetylation status and chimeric embryo complementation.Reproduction,133(1):219-230
Yang L, Chavatte-Palmer P, Kubota C, O'Neill M, Hoagland T, Renard J P, Taneja M, Yang X Z, and TianX C.2005. Expression of imprinted genes is aberrant in deceased newborn cloned calves andrelatively normal in surviving adult clones. Molecular Reproduction and Development,71(4):431-438
Yang X, Feng M, Jiang X, Wu Z, Li Z, Aau M, and Yu Q.2009. miR-449a and miR-449b are directtranscriptional targets of E2F1and negatively regulate pRb–E2F1activity through a feedback loopby targeting CDK6and CDC25A. Genes&Development,23(20):2388-2393
Yang X, and Seto E.2007. HATs and HDACs: from structure, function and regulation to novel strategiesfor therapy and prevention. Oncogene,26(37):5310-5318
Yang X J, and Seto E.2008. The Rpd3/Hda1family of lysine deacetylases: from bacteria and yeast to miceand men. Nature Reviews Molecular Cell Biology,9(3):206-218
Yang X Z, Smith S L, Tian X C, Lewin H A, Renard J P, and Wakayama T.2007b. Nuclear reprogrammingof cloned embryos and its implications for therapeutic cloning. Nature Genetics,39(3):295-302
Young L E, Fernandes K, McEvoy T G, Butterwith S C, Gutierrez C G, Carolan C, Broadbent P J,Robinson J J, Wilmut I, and Sinclair K D.2001. Epigenetic change in IGF2R is associated withfetal overgrowth after sheep embryo culture. Nature Genetics,27(2):153-154
Yeh E T H.2009. SUMOylation and De-SUMOylation: wrestling with life's processes. Journal ofBiological Chemistry,284(13):8223-8227
Zawada W M, Cibelli J B, Choi P K, Clarkson E D, Golueke P J, Witta S E, Bell K P, Kane J, de Leon F AP, Jerry D J, Robl J M, Freed C R, and Stice S L.1998. Somatic cell cloned transgenic bovineneurons for transplantation in parkinsonian rats. Nature Medicine,4(5):569-574
Zemach A, McDaniel I E, Silva P, and Zilberman D.2010. Genome-wide evolutionary analysis ofeukaryotic DNA methylation. Science,328(5980):916-919
Zhang M, Wang F C, Kou Z H, Zhang Y, and Gao S R.2009. Defective Chromatin Structure in SomaticCell Cloned Mouse Embryos. Journal of Biological Chemistry,284(37):24981-24987
Zhang X, Yazaki J, Sundaresan A, Cokus S, Chan S W L, Chen H, Henderson I R, Shinn P, Pellegrini M,and Jacobsen S E.2006. Genome-wide high-resolution mapping and functional analysis of DNAmethylation in Arabidopsis. Cell,126(6):1189-1201
Zhang Y H, Li J, Villemoes K, Pedersen A M, Purup S, and Vajta G.2007. An epigenetic modifier results inimproved in vitro blastocyst production after somatic cell nuclear transfer. Cloning and Stem Cells,9(3):357-363
Zhao J, Hao Y, Ross J W, Spate L D, Walters E M, Samuel M S, Rieke A, Murphy C N, and Prather R S.2010. Histone deacetylase inhibitors improve in vitro and in vivo developmental competence ofsomatic cell nuclear transfer porcine embryos. Cellular Reprogramming,12(1):75-83
Zhao J G, Ross J W, Hao Y H, Spate L D, Walters E M, Samuel M S, Rieke A, Murphy C N, and Prather RS.2009. Significant Improvement in Cloning Efficiency of an Inbred Miniature Pig by HistoneDeacetylase Inhibitor Treatment after Somatic Cell Nuclear Transfer. Biology of Reproduction,81(3):525-530
Zhou Q, Chipperfield H, Melton D A, and Wong W H.2007. A gene regulatory network in mouseembryonic stem cells. Proceedings of the National Academy of Sciences,104(42):16438-16443
Zhou Q, Renard J P, Le Friec G, Brochard V, Beaujean N, Cherifi Y, Fraichard A, and Cozzi J.2003.Generation of fertile cloned rats by regulating oocyte activation. Science,302(5648):1179-1179
Zhou W, Xiang T, Walker S, Farrar V, Hwang E, Findeisen B, Sadeghieh S, Arenivas F, Abruzzese R V, andPolejaeva I.2008. Global gene expression analysis of bovine blastocysts produced by multiplemethods. Molecular Reproduction and Development,75(5):744-58
Zuccotti M, and Monk M.1995. Methylation of the Mouse Xist Gene in Sperm and Eggs Correlates withImprinted Xist Expression and Paternal X-Inactivation. Nature Genetics,9(3):316-320