鸭CD8α基因的克隆与表达调控初步分析
摘要
我国是养鸭大国,占全世界养殖量70%以上。但随着养殖量的增加,鸭的病毒性疾病逐年增加,并日趋复杂,给养鸭业带来了巨大的损失。病毒性雏鸭肝炎是一种主要侵害3周龄以内的雏鸭的疾病,在病毒感染过程中,主要侵害T淋巴细胞。CD8作为T淋巴细胞表面的重要标志物,在抗病毒感染和细胞免疫体系中起着非常重要的作用。CD8α参与胸腺分化以及T细胞活化的信号传导,而CD8β主要协助CD8α发挥生物学功能。
已有研究证明,CD8α基因表达的调节可能存在包括CD8α特异性增强子和可能的沉默子在内的多种顺式调控元件和反式作用因子。CD8α基因DNA甲基化的改变也受胸腺高移动性型框蛋白和IL4等多种因子影响,从而导致基因表达的变化或异常表达。而关于鸭的CD8α基因转录调控和表观遗传调控至今尚不清楚。
本研究通过构建Ⅰ型雏鸭病毒肝炎感染模型,在成功克隆鸭CD8α基因cDNA序列和启动子区的基础上,对CD8α基因的表达特性和表达调控进行了初步分析,其主要研究结果如下：
1.分别以金定鸭、樱桃谷北京鸭、番鸭、绿头鸭和斑嘴鸭的脾脏组织cDNA为模板进行RT-PCR扩增,成功获得了金定鸭、樱桃谷北京鸭、番鸭、绿头鸭和斑嘴鸭CD8α基因CDS区,其长度都为714bp。同时采用RACE技术克隆了金定鸭CD8a cDNA全序列,长为1624bp,包括61bp的5'UTR,849bp的3'UTR,714bp的开放阅读框(ORF)。同时检测了雏鸭肝炎易感组、抗性组和对照组的鸭CD8α编码序列,发现三者间主要突变发生在外显子2。
2.以金定鸭、樱桃谷北京鸭、番鸭、绿头鸭和斑嘴鸭基因组DNA为模板,成功获得了金定鸭、樱桃谷北京鸭、番鸭、绿头鸭和斑嘴鸭基因(包含全部编码区和所有内含子,去除5’和3’非编码区序列)其CD8α基因编码区序列长分别为6568bp、6567bp、6488bp、6568bp和6577bp,都由6个外显子和5个内含子组成,除第一内含子外,其他内含子均符合"gt-ag"剪切法则。
3.对不同禽类(金定鸭、樱桃谷北京鸭、番鸭、绿头鸭、斑嘴鸭、家鸡、红色原鸡、斑胸草雀和火鸡)CD8α基因编码序列进行了进化分析,樱桃谷北京鸭与绿头鸭氨基酸同源性最高达100%,同源性最低的是番鸭与家鸡,为61.3%；且在胞外区还发现了Cys49、Cys119、Cys182等3个保守性氨基酸残基；在蛋白质级结构上,9条序列的α螺旋和β折叠亦相似,说明在禽类中CD8α进化是相当保守的。
4.通过RT-PCR和RT-qPCR,对鸭肌肉、肺、肝、大脑、小脑、胸腺、脾、肾脏和淋巴细胞等组织和细胞进行CD8α mRNA半定量和定量检测,发现鸭CD8α基因在胸腺、脾、肺和淋巴细胞中表达量较高,其次为肝、小脑和肾,肌肉和大脑中表达量最低。同时通过原位杂交技术检测了脾脏组织CD8α mRNA分布,发现鸭CD8α在脾脏白髓内阳性细胞分布密集,且易感组阳性细胞明显多于空白组。通过免疫组化技术检测了CD8α蛋白表达,发现在鸭脾脏白髓区的脾小结和淋巴鞘CD8α蛋白表达丰富。
5.分别采用Ⅰ型雏鸭肝炎病毒和Poly(I:C)接种3日龄雏鸭,利用RT-qPCR对感染后鸭的胸腺、脾、肺等组织时空表达谱进行分析,发现各组织CD8α基因总体表现为先上升,48h下降至最低值,48h后又有上升趋势。同时采用ELISA技术检测了血清IFN-α等细胞因子变化情况,发现IFN-α、IFN-γ变化趋势与CD8α基因表达趋势一致。
6.通过构建重组真核表达质粒pEGFP-C1-CD8α,对CD8α蛋白进行亚细胞定位分析,荧光显微镜观测结果显示,重组的EGFP-CD8α融合蛋白主要分布于NIT-3T3的细胞质中。
7.运用基因组步移扩增,成功克隆了鸭CD8α基因5'端2480bp的片段,包括第一外显子56bp,启动子区2424bp,使用在线软件(http://www.cbrc.jp/research/db/TFSEARCH.html)分析鸭CD8α基因启动子区域,发现了Nkx-2、GATA-1、GATA-3、GATA-1、NKX-2、AP-1等多个与细胞增殖、细胞凋亡以及病变过程相关的潜在转录因子结合位点。
8.通过制备一系列启动子缺失突变体(-625/-1bp,-1110/-1bp,-1413/-1bp,-2151/-1bp),定向亚克隆至荧光素酶表达载体pGL3-Basic中,通过荧光发光仪检测发现,-625～-1110启动子活性最强,且-625～-1bp区域和-625～-1110均存在着正调控元件。并对易感组、抗性组和对照组CD8α启动子区转录活性区序列进行了比较,发现在不同处理组间存在3处碱基突变(-985T>C、-552G>A、-482G>A),其中,-985T>C突变导致易感组的CD8α基因增加1个MZF1转录因子结合位点,-552G>A突变导致易感组和抗性组的CD8α基因减少1个CpG岛位点。
9.通过亚硫酸盐测序比较了雏鸭肝炎易感组、抗性组和对照组血液的CD8α基因的甲基化程度,发现易感组CD8α基因甲基化明显偏高(0.90±0.10),但与抗性组(0.73±0.15)和对照组(0.77±0.06)差异不显著(P>0.05)。且发现了第二个CpG位点上,在易感组中呈高度甲基化,而在抗性组和对照组的甲基化程度较低。
10.采用MethylFlash整体甲基化定量试剂盒对易感组、抗性组和对照组整体甲基化水平进行检测,结果表明,易感组血液整体甲基化水平要显著高于抗性组和对照组(P<0.05)。
With the farming output and consumption increasingly growing in duck industry, the viral disease of duck becomes serious and complicated year by year, which resulted in the huge losses to the duck industry. CD8molecule is a double strand glycoprotein existed on the surface of T cell, which composes of two dissimilar subunits CD8a and CD8β.It is also a major marker on the surface of the T lymphocyte surface, which plays an important role in the immune defense of mammals and birds. The CD8a gene takes part in thymus differentiation and signal transduction during T cell activated, while the CD8β only assisted with the CD8a to play biological functions.
The study has been demonstrated that the CD8a gene expression was regulated by CD8α-specific enhancer and silencer. Another study has been demonstrated that DNA methylation of CD8a gene affected by some factors, such as the thymus high mobility box protein and IL4, which resulted in abnormal expression. However, duCD8a gene involved in transcriptional regulation and epigenetic regulation was not been descripted up to date.
In this study, the sequence of cDNA and the promoter in duCD8a gene were cloned, and expression regulation was analyzed by disease model infected duckling virus hepatitis, its results are as follows:
The coding sequence (CDS) of CD8a from Jinding duck, Cherry Valley Peking duck, Muscovy, mallard and spot-billed duck were obtained by RT-PCR from their spleen, whose length is about714bp. And the cDNA sequence was cloned by RACE, which including the5'UTR of61bp, the3'UTR of849bp, the open reading frame of714bp. Besides, The CDS of CD8a was compared among susceptible group, resistant group and control group treated with duckling virus hepatitis, the nucleotide differences existed in exon2.
The CD8a gene of Jinding duck, Cherry Valley duck, muscovy, mallard and spot-billed duck was cloned and genomic organization was analyzed. The CD8a gene among5populations all composed of six exons and five introns, and all the boundary of exon/intron has GT/AG conserved sequences except the first intron. but their length was different, which spanned6568bp,6567bp,6488bp,6568bp and6577bp, respectively.
The phylogeny of CD8a gene was analyzed in different poultry(Jinding duck, Cherry Valley Peking duck, muscovy, mallard, spot-billed duck, domestic chicken, red Jungle fowl, zebra finch and turkey). The results indicated that the amino acid sequence showed the highest degree of identity between Cherry Valley Peking duck and mallard, and the lowest degree of identity between muscovy and domestic chicken. In addition, three conserved amino acid residues(Cys49, Cysl19and Cysl82) were discovered. Finally, the a-helices and p-strands in the structure of protein were also similar, which showed that CD8a evolution was very conservative in poultry.
The expression of CD8a mRNA in some organs and cells of duck (The muscle, lung, liver, brain, cerebellum, thymus, spleen, kidney, lymphocytes) was detected by RT-PCR and real-time RT-PCR, which revealed that the CD8mRNA was much higher in the thymus spleen, lung and lymphocytes than in other organs and the expression level was the lowest in muscle and brain. CD8a mRNA was identified on white pulp of spleen by in situ hybridization, and positive cells of the susceptible group were more obvious than the control group. CD8a molecular was detected identified on splenic corpuscle and periarterial lymphatic sheath of spleen by immunohistochemistry.
The CD8a mRNA levels were examined in some organs (such as cerebellum, thymus, spleen and so on) treated with polyriboinosinic polyribocytidylic acid (PolyⅠC) and duckling virus hepatitis. The result showed that the CD8mRNA levels was significantly down-regulated at48h compared to their levels at12h post-infection or24h post-infection with Polyl:C and duckling virus hepatitis (P<0.05). In addition, levels of cytokine (such as IFN-α、IFN-γ) were quantified using the ELISA kit. The result showed that both IFN-aand IFN-yhad a similar changing trend to CD8a mRNA expression.
The eukaryotic expression vector pEGFP-C1-CD8a was constructed and expressed in NIH-3T3cells successfully. EGFP-CD8a fusion protein was identified to locate at the membrane and cytoplasm of NIH-3T3cells.
The CD8a gene promoter was cloned by genome walking, the sequence of the promoter was analyzed by online software of bioinformatics (http://www.cbrc.jp/research/db/TFSEARCH.html) The DNA sequence of2480bp was amplified including56bp in exon1. And some transcriptional factor binding sites including CdxA、Nkx-2、GATA-1、SRY and so on were detected, whose function were relevance with cell proliferation, apoptosis.
The promoter missing mutants were constructed (-625/-1bp,-1110/-1bp,-1413/-1bp,-2151/-1bp) according to the sequence of CD8a gene promoter, and then subcloned into pGL3.2basic vectors to construct luciferase report gene vectors, respectively. The recombinant vectors were transfected into DT40cells with Lipofectamine2000, and the transcriptional activities were detected. The results indicated that CD8a gene promoter had obviously promoter activity. The sequence from-625to-1110of5'flanking region had the strongest promoter activities, including two positive (-625/-1and-625/-1110) regulatory domains. Then the sequence of regulatory domains in the susceptible group, the resistance group and control group was compared, three mutations (-985T>C,-552G>A,-484G>A)were found, which resulted in transcription factor binding sites increasing or CpG island reducing.
The CD8a gene methylation status of duck blood was compared. The results showed that CD8a gene methylation in the susceptible group was significantly higher than the other groups, but that difference was not significant (P>0.05). Meanwhile, the second CpG Island was found that methylation status was higher in the susceptible group than the other groups.
The global level of methylation in the susceptible ducks, the resistance ducks and control ducks were detected by MethyFlash Quantification Kit. The results showed that the global methylation level in the susceptible ducks was significantly higher than the resistance ducks and control ducks (P<0.05).
已有研究证明,CD8α基因表达的调节可能存在包括CD8α特异性增强子和可能的沉默子在内的多种顺式调控元件和反式作用因子。CD8α基因DNA甲基化的改变也受胸腺高移动性型框蛋白和IL4等多种因子影响,从而导致基因表达的变化或异常表达。而关于鸭的CD8α基因转录调控和表观遗传调控至今尚不清楚。
本研究通过构建Ⅰ型雏鸭病毒肝炎感染模型,在成功克隆鸭CD8α基因cDNA序列和启动子区的基础上,对CD8α基因的表达特性和表达调控进行了初步分析,其主要研究结果如下：
1.分别以金定鸭、樱桃谷北京鸭、番鸭、绿头鸭和斑嘴鸭的脾脏组织cDNA为模板进行RT-PCR扩增,成功获得了金定鸭、樱桃谷北京鸭、番鸭、绿头鸭和斑嘴鸭CD8α基因CDS区,其长度都为714bp。同时采用RACE技术克隆了金定鸭CD8a cDNA全序列,长为1624bp,包括61bp的5'UTR,849bp的3'UTR,714bp的开放阅读框(ORF)。同时检测了雏鸭肝炎易感组、抗性组和对照组的鸭CD8α编码序列,发现三者间主要突变发生在外显子2。
2.以金定鸭、樱桃谷北京鸭、番鸭、绿头鸭和斑嘴鸭基因组DNA为模板,成功获得了金定鸭、樱桃谷北京鸭、番鸭、绿头鸭和斑嘴鸭基因(包含全部编码区和所有内含子,去除5’和3’非编码区序列)其CD8α基因编码区序列长分别为6568bp、6567bp、6488bp、6568bp和6577bp,都由6个外显子和5个内含子组成,除第一内含子外,其他内含子均符合"gt-ag"剪切法则。
3.对不同禽类(金定鸭、樱桃谷北京鸭、番鸭、绿头鸭、斑嘴鸭、家鸡、红色原鸡、斑胸草雀和火鸡)CD8α基因编码序列进行了进化分析,樱桃谷北京鸭与绿头鸭氨基酸同源性最高达100%,同源性最低的是番鸭与家鸡,为61.3%；且在胞外区还发现了Cys49、Cys119、Cys182等3个保守性氨基酸残基；在蛋白质级结构上,9条序列的α螺旋和β折叠亦相似,说明在禽类中CD8α进化是相当保守的。
4.通过RT-PCR和RT-qPCR,对鸭肌肉、肺、肝、大脑、小脑、胸腺、脾、肾脏和淋巴细胞等组织和细胞进行CD8α mRNA半定量和定量检测,发现鸭CD8α基因在胸腺、脾、肺和淋巴细胞中表达量较高,其次为肝、小脑和肾,肌肉和大脑中表达量最低。同时通过原位杂交技术检测了脾脏组织CD8α mRNA分布,发现鸭CD8α在脾脏白髓内阳性细胞分布密集,且易感组阳性细胞明显多于空白组。通过免疫组化技术检测了CD8α蛋白表达,发现在鸭脾脏白髓区的脾小结和淋巴鞘CD8α蛋白表达丰富。
5.分别采用Ⅰ型雏鸭肝炎病毒和Poly(I:C)接种3日龄雏鸭,利用RT-qPCR对感染后鸭的胸腺、脾、肺等组织时空表达谱进行分析,发现各组织CD8α基因总体表现为先上升,48h下降至最低值,48h后又有上升趋势。同时采用ELISA技术检测了血清IFN-α等细胞因子变化情况,发现IFN-α、IFN-γ变化趋势与CD8α基因表达趋势一致。
6.通过构建重组真核表达质粒pEGFP-C1-CD8α,对CD8α蛋白进行亚细胞定位分析,荧光显微镜观测结果显示,重组的EGFP-CD8α融合蛋白主要分布于NIT-3T3的细胞质中。
7.运用基因组步移扩增,成功克隆了鸭CD8α基因5'端2480bp的片段,包括第一外显子56bp,启动子区2424bp,使用在线软件(http://www.cbrc.jp/research/db/TFSEARCH.html)分析鸭CD8α基因启动子区域,发现了Nkx-2、GATA-1、GATA-3、GATA-1、NKX-2、AP-1等多个与细胞增殖、细胞凋亡以及病变过程相关的潜在转录因子结合位点。
8.通过制备一系列启动子缺失突变体(-625/-1bp,-1110/-1bp,-1413/-1bp,-2151/-1bp),定向亚克隆至荧光素酶表达载体pGL3-Basic中,通过荧光发光仪检测发现,-625～-1110启动子活性最强,且-625～-1bp区域和-625～-1110均存在着正调控元件。并对易感组、抗性组和对照组CD8α启动子区转录活性区序列进行了比较,发现在不同处理组间存在3处碱基突变(-985T>C、-552G>A、-482G>A),其中,-985T>C突变导致易感组的CD8α基因增加1个MZF1转录因子结合位点,-552G>A突变导致易感组和抗性组的CD8α基因减少1个CpG岛位点。
9.通过亚硫酸盐测序比较了雏鸭肝炎易感组、抗性组和对照组血液的CD8α基因的甲基化程度,发现易感组CD8α基因甲基化明显偏高(0.90±0.10),但与抗性组(0.73±0.15)和对照组(0.77±0.06)差异不显著(P>0.05)。且发现了第二个CpG位点上,在易感组中呈高度甲基化,而在抗性组和对照组的甲基化程度较低。
10.采用MethylFlash整体甲基化定量试剂盒对易感组、抗性组和对照组整体甲基化水平进行检测,结果表明,易感组血液整体甲基化水平要显著高于抗性组和对照组(P<0.05)。
With the farming output and consumption increasingly growing in duck industry, the viral disease of duck becomes serious and complicated year by year, which resulted in the huge losses to the duck industry. CD8molecule is a double strand glycoprotein existed on the surface of T cell, which composes of two dissimilar subunits CD8a and CD8β.It is also a major marker on the surface of the T lymphocyte surface, which plays an important role in the immune defense of mammals and birds. The CD8a gene takes part in thymus differentiation and signal transduction during T cell activated, while the CD8β only assisted with the CD8a to play biological functions.
The study has been demonstrated that the CD8a gene expression was regulated by CD8α-specific enhancer and silencer. Another study has been demonstrated that DNA methylation of CD8a gene affected by some factors, such as the thymus high mobility box protein and IL4, which resulted in abnormal expression. However, duCD8a gene involved in transcriptional regulation and epigenetic regulation was not been descripted up to date.
In this study, the sequence of cDNA and the promoter in duCD8a gene were cloned, and expression regulation was analyzed by disease model infected duckling virus hepatitis, its results are as follows:
The coding sequence (CDS) of CD8a from Jinding duck, Cherry Valley Peking duck, Muscovy, mallard and spot-billed duck were obtained by RT-PCR from their spleen, whose length is about714bp. And the cDNA sequence was cloned by RACE, which including the5'UTR of61bp, the3'UTR of849bp, the open reading frame of714bp. Besides, The CDS of CD8a was compared among susceptible group, resistant group and control group treated with duckling virus hepatitis, the nucleotide differences existed in exon2.
The CD8a gene of Jinding duck, Cherry Valley duck, muscovy, mallard and spot-billed duck was cloned and genomic organization was analyzed. The CD8a gene among5populations all composed of six exons and five introns, and all the boundary of exon/intron has GT/AG conserved sequences except the first intron. but their length was different, which spanned6568bp,6567bp,6488bp,6568bp and6577bp, respectively.
The phylogeny of CD8a gene was analyzed in different poultry(Jinding duck, Cherry Valley Peking duck, muscovy, mallard, spot-billed duck, domestic chicken, red Jungle fowl, zebra finch and turkey). The results indicated that the amino acid sequence showed the highest degree of identity between Cherry Valley Peking duck and mallard, and the lowest degree of identity between muscovy and domestic chicken. In addition, three conserved amino acid residues(Cys49, Cysl19and Cysl82) were discovered. Finally, the a-helices and p-strands in the structure of protein were also similar, which showed that CD8a evolution was very conservative in poultry.
The expression of CD8a mRNA in some organs and cells of duck (The muscle, lung, liver, brain, cerebellum, thymus, spleen, kidney, lymphocytes) was detected by RT-PCR and real-time RT-PCR, which revealed that the CD8mRNA was much higher in the thymus spleen, lung and lymphocytes than in other organs and the expression level was the lowest in muscle and brain. CD8a mRNA was identified on white pulp of spleen by in situ hybridization, and positive cells of the susceptible group were more obvious than the control group. CD8a molecular was detected identified on splenic corpuscle and periarterial lymphatic sheath of spleen by immunohistochemistry.
The CD8a mRNA levels were examined in some organs (such as cerebellum, thymus, spleen and so on) treated with polyriboinosinic polyribocytidylic acid (PolyⅠC) and duckling virus hepatitis. The result showed that the CD8mRNA levels was significantly down-regulated at48h compared to their levels at12h post-infection or24h post-infection with Polyl:C and duckling virus hepatitis (P<0.05). In addition, levels of cytokine (such as IFN-α、IFN-γ) were quantified using the ELISA kit. The result showed that both IFN-aand IFN-yhad a similar changing trend to CD8a mRNA expression.
The eukaryotic expression vector pEGFP-C1-CD8a was constructed and expressed in NIH-3T3cells successfully. EGFP-CD8a fusion protein was identified to locate at the membrane and cytoplasm of NIH-3T3cells.
The CD8a gene promoter was cloned by genome walking, the sequence of the promoter was analyzed by online software of bioinformatics (http://www.cbrc.jp/research/db/TFSEARCH.html) The DNA sequence of2480bp was amplified including56bp in exon1. And some transcriptional factor binding sites including CdxA、Nkx-2、GATA-1、SRY and so on were detected, whose function were relevance with cell proliferation, apoptosis.
The promoter missing mutants were constructed (-625/-1bp,-1110/-1bp,-1413/-1bp,-2151/-1bp) according to the sequence of CD8a gene promoter, and then subcloned into pGL3.2basic vectors to construct luciferase report gene vectors, respectively. The recombinant vectors were transfected into DT40cells with Lipofectamine2000, and the transcriptional activities were detected. The results indicated that CD8a gene promoter had obviously promoter activity. The sequence from-625to-1110of5'flanking region had the strongest promoter activities, including two positive (-625/-1and-625/-1110) regulatory domains. Then the sequence of regulatory domains in the susceptible group, the resistance group and control group was compared, three mutations (-985T>C,-552G>A,-484G>A)were found, which resulted in transcription factor binding sites increasing or CpG island reducing.
The CD8a gene methylation status of duck blood was compared. The results showed that CD8a gene methylation in the susceptible group was significantly higher than the other groups, but that difference was not significant (P>0.05). Meanwhile, the second CpG Island was found that methylation status was higher in the susceptible group than the other groups.
The global level of methylation in the susceptible ducks, the resistance ducks and control ducks were detected by MethyFlash Quantification Kit. The results showed that the global methylation level in the susceptible ducks was significantly higher than the resistance ducks and control ducks (P<0.05).
引文
[1]龚非力.医学免疫学(第二版),北京：科学出版社,2000
[2]Bernard A Boumsell L. The clusters of differentiation (CD) defined by the First International Workshop on human leucocyte differentiation antigens. Hum Immunol,1984,11 (1):1-10
[3]杨汉春.动物免疫学(第二版),北京：中国农业大学出版社,2003
[4]廖定为,唐秀山,蒋一男,等.北京鸭CD8α分子克隆与表达及其多克隆抗体制备,中国兽医杂志,2008,44(6)：5-7
[5]白家媛.樱桃谷北京鸭CD8α胞外区多肽的原核表达、抗体制备及初步应用,华中农业大学硕士学位论文,2010
[6]Sonja Kothlowa, Nina K. Mannesb, Beatrice Schaerera, et al. Characterization of duck leucocytes by monoclonal antibodies. Dev Comp Immunol,2005,29:733-748
[7]廖定为.鸭CD8α分子克隆与多克隆抗体制备及MHC I和β2m的表达,北京：中国农业大学学位论文,2007
[8]Dembic Z, Haas W, Zamoyska R et al. Transfection of the CD8 gene enhances T-cell recognition. Nature,1987,326:510-511
[9]Luhtala M. Chicken CD4, CD8αβ,CD8aa T cell coreceptor molecules. Poultry science.1998, 77:1858-1873
[10]Urner J M, Brodsky M H, Irving B A, et al. Interaction of the N-terminal region of tyrosine kinase p561ck with cytoplasmic domain of CD4 and CD8 is mediated by cysteine motifs. Cell, 1990,60(5):755-765
[11]Luhtala M. Avian CD4, CD8aa and CD8αβ T cell coreceptor molecules. Turku Finland. Annales Universitat&Turkuensis,1997,274:1-95
[12]李卫,白家媛,许媛媛,等.麻鸭和樱桃谷北京鸭的CD3ω、CD4、CD8a基因ORF克隆及序列分析.中国农业科学,2009,42(12)：4428-4434
[13]Z. LI, K. E. NESTOR, Y. M SAIF, et al. Cross-Reactive Anti-Chicken CD4 and CD8 Monoclonal Antibodies Suggest Polymorphism of the Turkey CD8a Molecule. Poultry Science,1999,78:1526-1531
[14]胡青海,焦新安,潘志明,等.中国部分地方品种鸡CD4和CD8a基因cDNA的克隆与序列分析,畜牧兽医学报,2006,37(3)：216-221
[15]Luhtala M, Tregaskes C A, Young J, et al. Polymorphism of chicken CD8-alpha, but not CD8-beta. Immunogenetics,1997,46:396-401
[16]孔令敏.CD147基因的转录调控机制及其表观遗传修饰,第四军医大学学位论文,2010
[17]Vaquerizas J M, Kummerfeld S K, Teichmann SA, et al. A census of human transcription factors:function, expression and evolution. Nat Rev Genet,2009,10(4):252-263
[18]章成,史冬燕,曾黎琼,等.真核生物转录调控的研究进展.云南农业大学学报,2007,22：164-176
[19]刘德培,查锡良,药立波.医学分子生物学,北京：人民卫生出版社,2006
[20]Dever T E. Gene-specific regulation by general translation factors. Cell,2002,108(4):545-56
[21]Emerson B M. Specificity of gene regulation. Cell,2002.109(3):267-270
[22]Hobert. Common logic of transcription factor and microRNA action. Trends Biochem Sci, 2004,29:462
[23]M. Ptashne, A. Gann. Genes and Signals (Cold Spring Harbor Laboratory, Cold Spring Harbor, NY,2002
[24]Grimson A, Farh K K, Johnston W K, et al. MicroRNA targeting specificity in mammals: determinants beyond seed pairing. Mol. Cell,2007,27:91
[25]Pal Saetrom, Bret S E Heale, Ola Snove J et al. Distance constraints between microRNA target sites dictates efficacy and cooperativity. Nucleic Acids Res,2007,35:23-33
[26]Buck M J, Lieb J D. A chromatin-mediated mechanism for specification of conditional transcription factor targets. Nat. Genet,2006,38:1446
[27]Martijn Kedde, Markus J. Strasser, Bijan Boldajipour, et al. RNA-Binding Protein Dndl Inhibits MicroRNA Access to Target mRNA. Cell,2007,131:1273
[28]Robins H, Li Y. Padgett R W, Predicting microRNA Targets with High Precision. Proc. Natl. Acad.Sci,2005.102:4006
[29]Vasudevan S. Tong. Y J, Steitz A. Switching from Repression to Activation:MicroRNAs Can Up-Regulate Translation. Science,2007,31(8):19-31
[30]Pillai R S, Bhattacharyya S N, Filipowicz W. Repression of protein synthesis by miRNAs: how many mechanisms? Trends Cell Biol,2007,17:118
[31]Gray S, Levine M. Transcriptional repression in development. Curr Cell Biol,1996,8:358
[32]Davidson E H, Genomic Regulatory Systems, Academic Press, San Diego, CA,2001
[33]Alon U, An Introduction to Systems Biology:Design Principles of Biological Circuits (Chapman & Hall/CRC), Boca Raton, FL,2006
[34]Johnston R J, Chang S Jr, Etchberger J F, et al. MicroRNAs acting in a double-negative feedback loop to control a neuronal cell fate decision. Proc. Natl. Acad. Sci,2005, 102:124-149
[35]Tsang J, Zhu J, Oudenaarden van A. MicroRNA-mediated feedback and feedforward loops are recurrent network motifs in mammals. Mol.Cell,2007,26:753
[36]Thomson J M, Michael Thomson, Parker Joel S, et al. Extensive post-transcriptional regulation of microRNAs and its implications for cancer. Genes Dev,2006,20:2202
[37]Lee E J, Baek M, Gusev Y, et al. Systematic evaluation of microRNA processing patterns in tissues, cell lines, and tumors. RNA,2007,14:35
[38]Kawahara Y, Zinshteyn B, Sethupathy P, et al. Redirection of silencing targets by adenosine-to-inosine editing of miRNAs. Science,2007,315:1137
[39]Wray G A, Hahn M W, Abouheif E, et al. The evolution of transcriptional regulation in eukaryotes. Mol. Biol Evol,2003,20:1377
[40]Ellmeier W, Sawada S and Littman D R. The regulation of CD4 and CD8 coreceptor gene expression during T cell development. Annu. Rev. Immunol,1999,17:523
[41]Hostert A, Tolaini M, Festenstein, R, et al. A CD8 genomic fragment that directs subset-specific expression of CD8 in transgenic mice. J. Immunol.1997,158:4270
[42]Zhang X L, Seong R, Piracha R, et al. Distinct stage-specific cis-active transcriptional mechanisms control expression of T cell coreceptor CD8 alpha at double-and single-positive stages of thymic development. Immunol,1998,161:2254
[43]Ellmeier W, Sunshine M J, Losos K, et al. Multiple developmental stage-specific enhancers regulate CD8 expression in developing thymocytes and in thymus-independent T cells. Immunity,1998,9:485
[44]Taniuchi I, Ellmeier W and Littman D R. The CD4/CD8 lineage choice:New insights into epigenetic regulation during T cell development. Adv. Immunol,2004,83:55
[45]Ktistaki E, Garefalaki A, Williams A, et al. CD8 locus nuclear dynamics during thymocyte development. Immunol,2010,184:56-86
[46]Ellmeier W, Sunshine M J, Maschek R, et al. Combined deletion of CD8 locus cis-regulatory elements affects initiation but not maintenance of CD8 expression. Immunity.2002,16:623
[47]Feik N, Bilic I, Tinhofer J, et al. Functional and molecular analysis of the double-positive stage-specific CD8 enhancer E8Ⅲ during thymocyte development. J. Immunol,2005,174: 1513
[48]Chi T H, Wan M, Zhao K, et al. Reciprocal regulation of CD4/CD8 expression by SWI/SNF-like BAF complexes. Nature,2002,418:195
[49]Bilic I, Koesters C, Unger B, et al. Negative regulation of CD8 expression via Cd8 enhancer-mediated recruitment of the zinc finger protein MAZR. Nat. Immunol,2006,7:392
[50]Lee P P, Fitzpatrick D R, Beard C, et al. A critical role for Dnmtl and DNA methylation in T cell development, function, and survival. Immunity,2001,15:763
[51]Ng S Y, Yoshida T and Georgopoulos K. Ikaros and chromatin regulation in early hematopoiesis. Curr. Opin. Immunol,2007,19:116
[52]Yasui Y, Miyano M, Cai S, et al. SATB1 targets chromatin remodelling to regulate genes over long distances. Nature,2002,419:641
[53]Nie H, Yao X, Maika S D, et al. SATB1 is required for CD8 coreceptor reversal. Mol. Immunol,2008,46:207
[54]Albu D I, Feng D, Bhattacharya D, etal. BCL11B is required for positive selection and survival of double-positive thymocytes. Exp. Med,2007,204:3003
[55]Trygve O Tollefsbol. Epigenetics Protocols. Totowa New Jersey:Humana Press,2004
[56]Esteller, M. Epigenetic gene silencing in cancer:the DNA hypermethylome. Hum. Mol. Genet,2007,16(1):50-59
[57]Lopez-Serra L and Esteller M. Proteins that bind methylated DNA and human cancer:reading the wrong words. Br. J. Cancer,2008,98:1881-1885
[58]Kuroda A, Rauch A T, Todorov I, et al. Insulin gene expression is regulated by DNA methylation. PLoS ONE,2009,4:95
[59]Thomson J P, Skene P J, Selfridge J, et al. CpG islands influence chromatin structure via the CpG-binding protein Cfpl. Nature,2010,464:1082-1086
[60]Comb M, Goodman H M. CpG methylation inhibits proenkephalin gene expression and binding of the transcription factor AP-2. Nucleic Acids Res,1990,18(13):3975-3982
[61]Prendergast G C, Lawe D, Ziff E B. Association of Myn, the murine homolog of max, with c-Myc stimulates methylation-sensitive DNA binding and ras cotransformation. Cell,1991 May 3,65(3):395-407
[62]Mancini D N, Rodenhiser D I, Ainsworth P J, et al. CpG methylation within the 5'regulatory region of the BRCA1 gene is tumor specific and includes a putative CREB binding site. Oncogene,1998,16(9):1161-1169
[63]Mancini D N, Singh S M, Archer T K, et al. Site-specific DNA methylation in the neurofibromatosis (NF1) promoter interferes with binding of CREB and SP1 transcription factors. Oncogene,1999,18(28):4108-4119
[64]Campanero M R, Armstrong M I, Flemington E K. CpG methylation as a mechanism for the regulation of E2F activity. Proc Natl Acad Sci USA,2000,97(12):6481-6486
[65]Robertson K D, Ait-Si-Ali S, Yokochi T, et al. DNMT1 forms a complex with Rb, E2F1 and HDAC1 and represses transcription from E2F-responsive promoters. Nat Genet,2000,25(3): 338-342
[66]Prokhortchouk A, Hendrich B, Jorgensen H, et al. The pi20 catenin partner Kaiso is a DNA methylation-dependent transcriptional repressor. Genes Dev,2001,15(13):1613-1618
[67]Prokhortchouk E, Hendrich B. Methyl-CpG binding proteins and cancer:are MeCpGs more important than MBDs? Oncogene,2002,21(35):5394-5399
[68]Wolffe A P. Packaging principle:how DNA methylation and histone acetylation control the transcriptional activity of chromatin. Exp Zool.1998,282(1-2):239-244
[69]Kundu T K, Rao M R. CpG islands in chromatin organization and gene expression. J Biochem,1999,125(2):217-222
[70]Nakao M. Epigenetics:interaction of DNA methylation and chromatin. Gene,2001,278(1-2): 25-31
[71]Jiang C D, Deng C Y, Xiong Y Z. Patterns of cytosine methylation in parental lines and their hybrids of Large White and Meishan reciprocal crosses. Agricultural Science in China,2004, 3(1):57-63
[72]Xu Q, Zhang Y, Sun D, et al. Analysis on DNA methylation of various tissues in chicken [J]. Anim Biotechnol,2007,18(4):231-241
[73]徐青.鸡DNA甲基化组织特异性及亲本与子代甲基化差异性研究,北京：中国农业大学博十学位论文,2006
[74]林莉.体细胞克隆牛功能基因DNA甲基化及其表达差异,北京：中国农业大学博士学位论文,2007
[75]Cockett N E, Shay T L, Green R D et al. Rapid communications Taq1 restriction fragment length polymorphism in the bovine calpastatin gene. Anim Sci,1995,73(12):3790
[76]Timothy A H, Robert W R and Jennifer A M G. Construction and evolution ofimprinted loci in mammals. Trends in Genetics,2007,23(9):440-448
[77]张立岭,林花,杨丽君.蒙古羊胸椎数的亲本印记遗传研究.内蒙古农业大学学报,2000,21(2)：1-6
[78]Noyer J L, Causse S, Tomekpe K, et al. A new image of plantain diversity assessed by SSR, AFLP and MSAP markers. Genetica,2005,124(1):61-69
[79]洪柳,邓秀新.应用MASP技术对脐橙品种进行DNA甲基化分析.中国农业科学,2005,38(11)：2301-2307
[80]W ilson A S, Power B E and Molloy P L. DNA hypomethylation and human diseases. Biochim. Biophys. Acta,2007,1775:138-162
[81]Ito Y, Koessler T, Ibrahim A E K, et al. Somatically acquired hypomethylation of IGF2 in breast and colorectal cancer. Hum. Mol. Genet,2008,17:2633-2643
[82]Lujambio, A. Ropero S, Ballestar E, et al. Genetic unmasking of an epigenetically silenced microRNA in human cancer cells. Cancer Res,2007,67:1424-1429
[83]Lujambio A, Calin G A, Villanueva A, et al. A microRNA DNA methylation signature for human cancer metastasis. Proc. Natl. Acad. Sci,2008, USA 105:13556-13561
[84]Chahrour M, Jung SY, Shaw C, et al. MeCP2, a key contributor to neurological disease, activates and represses transcription. Science,2008,320:1224-1229
[85]Urdinguio RG, Sanchez-Mut J V, Esteller M. Epigenetic mechanisms in neurological diseases: genes, syndromes, and therapies. Lancet Neurol.2009,8:1056-1072
[86]Robertson K D. DNA methylation and human disease. Nat. Rev. Genet,2005,6:597-610
[87]Jin B, Li Q, Zhang L, et al. DNA methyl transferase 3B (DNMT3B) mutations in 1CF syndrome lead to altered epigenetic modifications and aberrant expression of genes regulating development, neurogenesis and immune function. Hum. Mol. Genet,2008,17:690-709
[88]Pan W, Zhu S, Yuan M. et al. MicroRNA-21 and microRNA-148a contribute to DNA hypomethylation in lupus CD4+T cells by directly and indirectly targeting DNA methyl transferase. Immunol,2010,184:6773-6781
[89]Herman J q, Graff J R, Myohanen S, et al. Methlation 2 Specific PCR:A novel PCR assay for methylation status of CPG islands. Proc Natl Acad Sci, USA,1996,93(18):9821-9826
[90]张云,辛海明,刘泽军,等.p53凋亡刺激蛋白基因5'端非编码区CpG岛高甲基化与其mRNA表达的改变.第三军医大学学报,2005,27(21)：2103-2106
[91]Herman J G, Baylin S B. Methylation-specific PCR Current Protocols in Human Genetics, 1998,10(6):1-10
[92]凌飞.猪Myll与adiponectin基因启动子克隆及其表达调控研究,华南农业大学学位论文,2008
[93]肖正中.猪基因组甲基化位点的克隆及Lyn基因转录调控分析,华南农业大学学位论文,2009
[94]刘晓瑛,李金龙,傅业全,等.鸡马立克氏病肾肿瘤p15基因的甲基化特异性PCR检测,中国兽医科学,2010,40(01)：61-64
[95]Frommer M, MeDonald L E, Millar D S, et al., A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands. Proc Natl Acad Sci,1992,89(5):1827-1831
[96]林莉.体细胞克隆牛功能基因DNA甲基化及其表达差异,中国农业大学学位论文,2007
[97]荣美洁,李兰,董文娟,等.崂山奶山羊乳腺中孕激素受体基因甲基化与基因表达关系的研究,青岛农业大学学报(自然科学版)2010,27(3)：186-190
[98]白同,杨斌,娄诚,等.APC和CDKN2A基因甲基化定量分析对肝细胞癌的诊断价值,世界华人消化杂志,2009,17(29)：3001-3007
[99]周少贞,李相辉,张玉祥.EGFR基因启动子区甲基化状态分析,中国生物化学与分子生物学报,2010,26(6)：568-574
[100]SuY, Dodson M V, Li X B. The effects of dietary betaine supplementation on fatty liver performance, serum parameters, histological changes, methylation status and the mRNA expression level of Spotl4a in Landes goose fatty liver. Comparative Biochemistry and Physiology,2009,154:308-314
[101]赵贵森,郑海燕,莫耀南,等.一种用于DNA甲基化分析的改进型亚硫酸氢盐转化法,中国生物化学与分子生物学报,2007,23(10)：876-880
[102]张祖萍,脑胶质瘤的表观遗传学研究.中南人学博十学位论文,2009
[103]Xiong Z and Laird P W. COBRA:a sensitive and quantitative DNA methylation assay. Nucleic Acids Res,1997,25(12):2532-2534
[104]Brena R M, Auer H, Komacker K, et al. Accurate quantifcation of DNA methylation using combined bisulfite restricfion anlalysis coupled with the Agilent 2100 Bioanalyzer platform. Nucleic Acids Ras,2006,34(3):17
[105]Eads C A, Danenberg K D, Kawakami K, et al. MethyLight:a high-throughput assay to measure DNA methylation. Nucleic Acids Res,2000,28(8):32
[106]Wittwer C T, Gudrun H R, Cameron N G, et al. High-resolution genotyping by amplicon melting analysis using LCGreen. Clin Chem,2003,49(6):853-860
[107]李宏伟,李慎,梁平,等.焦磷酸测序检测RARβ2基因启动子甲基化方法的建立,第四军医大学学报,2009,30(14)：1285-1288
[108]Ying Y, Zhang H M, Tian F, et al. Quantitative Evaluation of DNA Methylation Patterns for ALVE and TVB Genes in a Neoplastic Disease Susceptible and Resistant Chicken Model. PLoS ONE,2008,3(3):1-10
[109]Luo J, Ying Y, Zhang H M, et al. Down-regulation of Promoter Methylation Level of CD4 gene after MDV Infection in MD-susception Chicken line. BioMed Central (BMC) Genetics, 2010, (5):25-31
[110]Kuo K C. McCune R A, Gehrke C W, et al. Quantitative reversed-phase high performance liquid chromatographic determination of major and modified deoxyribonucleosides in DNA, Nucleic Acids Res,1980,24; 8(20):4763-4776
[111]Mario F F, Esther U L, Borja D, et al. High-performance capillary electrophoretic method for the quantification of 5-methyl 2'-deoxycytidine in genomic DNA:Application to plant, animal and human cancer tissues. Electrophoresis,2002,23(11):1677-1681
[112]邓大君,邓国仁,吕有勇,等.变性高效液相色谱法检测CpG岛胞嘧啶甲基化.中华医学杂志,2001,80(2)：158-161
[113]Ramsahoye B H. Measurement of genome wide DNA methylation by eversed-phase high-performance liquid chromatography. Methods,2002,27:156-161
[114]蔡鑫泽,乔莹,都姝妍,等.反相高效液相色谱法测定人乳腺癌MCF7细胞中基因组DNA甲基化水平,中国医科大学学报,39(11)：898-903
[115]张俊杰,张立坚,刘春安,等.组织中全基因组DNA甲基化的液相色谱-串联质谱分析,质谱,2010,31(6)：326-330
[116]Liguo S, James S R, Kazim L, et al. Specific Method for the Determination of Genomic DNA Methylation by Liquid Chromatography-Electrospray Ionization Tandem Mass Spectrometry, Anal. Chem,2005,77:504-510
[117]Kelly M, Armstrong E N, Berminghaml S A, et al. Global DNA methylation measurement by HPLC using low amounts of DNA. Biotechnol. J,2011,6:113-117
[118]Jason W J, Harding K, David H B, et al. HPLC analysis of plant DNA methylation:a study of critical methodological factors. Plant Physiology and Biochemistry,2005,43:844-853
[119]梁秋菊,刘丽娜,彭健,等.猪血液和肌肉组织DNA甲基化含量的测定.中国农业科学.2007,40(8)：1774-1779
[120]尹慧,黄代新,翟仙敦,等.HPLC法检测人外周血5m C含量及其与年龄相关性研究,中国法医学杂志,2007,22(1)：8-11
[121]陈英.荣昌猪DNA甲基化水平的差异分析,西南大学学位论文,2009
[122]张志勇,李春宏,仇小强,等.广西长寿地区人群白细胞DNA总体甲基化水平研究,中国老年学杂志,2009,29：1513-1516
[123]宗凯,刘国庆,曹树青,等.日粮蛋氨酸和赖氨酸水平对肉鸡生长性能及肌肉和肝脏组织DNA甲基化含量的影响,粮食与饲料工业,2010,2：33-37
[124]万亚琴.DNA甲基化与肉牛杂种优势关系的初步研究,两南大学硕士学位论文,2008
[125]蒋曹德,邓昌彦,熊远著,等.DNA甲基化差异对猪生长性状的影响,畜牧兽医学报,2005,36(2)：105-110
[126]班谦,家鸡胚胎早期发育过程中DNA甲基化的MSAP分析,石河子大学,2009
[127]肖正中,刘小红,王翀,等.长白猪×蓝塘猪及其杂种基因组DNA甲基化分析,畜牧兽医学报,2011,42(5)：613-620
[128]唐韶青,张沅,徐青,等.不同动物部分组织基因组甲基化程度的差异分析,农业生物技术学报,2006,14(4)：507～510
[129]Xu Q, Zhang Y, Sun D, et al. Analysis on DNA methylation of various tissues in chicken. Anim Biotechnol,2007,18(4):231-241
[130]Chun Y, Zhang M J, Niu W P, et al. Analysis of DNA Methylation in Various Swine Tissues. PLoS ONE,2011,6(1):162
[131]徐青,张沅,孙东晓,等.应用MSAP方法检测鸡不同组织基因组的甲基化状态,遗传,2011,33(6)：620-626
[132]Tibor Rauch, Zunde Wang, Xinmin Zhang, et al. Homeobox gene methylation in lung cancer studied by genome-wide analysis with a microarray-based methylated CpG island recovery assay. Proc Natl Acad Sci U S A,2007,104(13):5527-5555
[133]Michael W, Jonathan J D, David W, et al. Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cells. Nat Genet,2005,37(8):853-862
[134]Zhang X Y, Yazaki J S, Sundaresan A, et al. Genome-wide high-resolution mapping and functional analysis of DNA methylation in arabidopsis. Cell,2006,126(6):1189-1201
[135]Lister R, Malley R C, Tonti-Filippini J, et al. Highly integrated single-base resolution maps of the epigenome in Arabidopsis. Cell,2008,133(3):523-536
[136]Yoshinao R, Yukako I, Fumiaki S, et al. Genome-wide analysis of aberrant methylation in human breast cancer cells using methyl-DNA immunoprecipitation combined with high-throughput sequencing. BMC Genomics,2010,11:137
[137]Li Q H, Li N, Hu X X, et al. Genome-Wide Mapping of DNA Methylation in Chicken. PLoS ONE,2011,6(5):1942
[138]Benjamin A F, Webste D R, Lee J H, et al. Direct detection of DNA methylation during single-molecule, real-time sequencing. Nature Methods 7,2010,1:461-465
[139]熊启香,熊莉娟.乙型肝炎病毒感染与肝细胞癌DNA甲基化研究进展,临床肝胆病杂志,2011,27(8)：881-884
[140]Ji C Z, Zong T Y, Jun L, et al. Persistent infection of hepatitis B virus is involved in high rate of p 16 methylation in hepatocelluarcarcinoma. Mol Carcinog,2006,45(7):530-536.
[141]Shim Y H, Yoon G S, Choi H J, et al. p16 Hypermethylation in theearly stage of hepatitis B virus -associated hepatocarcinogenesis. Cancer Lett,2003,190(2):213-219.
[142]Zhong S, Tang M W, Yeo W, et al. Intensive hypermethylation of theCpG island of Ras association domain family 1A in hepatit is B virus-associated hepatocellular carcinomas. Clin Cancer Res,2003,9(9):3376-3382.
[143]Zhong S, Tang M W, Yeo W, et al. S ilencing of G STP1 gene by CpG island DNA hypermethylation in HBV-associated hepatocellular carinomas. Clin Cancer Res,2002,8(4): 1087-1092.
[144]Yang B, Guo M, Herman J G, et al. Aberrant promoter methylatio nprofiles of tumor suppressor genes in hepatocellular carcinoma. Am J Pathol,2003,163(3):1101-1107.
[145]Wei Y, Van N, Prigent S, et al. Altered expression of E-cadherin in hepatocellular carcinoma:correlations with geneticalterations, beta-catenin expression, and clinical features. Hepatology,2002,36(3):692-701.
[146]郭朝阳.慢加急性肝衰竭患者外周血肿瘤坏死因子-α基因启动子甲基化状态的研究,山东大学硕士学位论文,2010
[147]于淑霞.IL-10在慢性乙型肝炎和慢加急性肝衰竭患者中启动子甲基化研究,山东大学硕士学位论文,2010
[148]李凤彩.慢加急性重型乙型病毒性肝炎患者血清IFN-γ水平及其启动子甲基化状态研究,山东大学硕士学位论文,2010
[149]张海元,云鹏.肝癌细胞系中Runx3基因表达及启动子区异常甲基化分析.长江大学学报(自然科学版),2009,36(1)：1-3
[150]Hammad H, Shinya S, Mari T, et al. Cd8 enhancer E8I and Runx factors regulate CD8a expression in activated CD8+T cells. PNAS,2011,108:18330-18335
[151]Flanagan B F, Wotton D, Tuck-Wah S, et al. DNase hypersensitivity and methylation of the human CD3G and D genes during T-cell development. Immunogenetics,1990,31(1):13-20
[152]Taylor K H, Liu.J. Guo J, et al. Promoter DNA methylation of CD10 in lymphoid malignancies. Leukemia,2006,20:1910-1912
[153]Guillermo G, Daniel J, Smith T L, et al. DNA Methylation of Multiple Promoter-associated CpG Islands in Adult Acute Lymphocytic Leukemia. Clin Cancer Res,2002,8:2217-2224.
[154]Schwab J and Illges H. Regulation of CD21 expression by DNA methylation and histone deacetylation. International Immunology,2001,13(5):705-710
[155]张勤,王金玉,主编.动物遗传育种研究最新进展论文集,2011
[156]Mariko W, Ogawal Y, Itoh K, et al. Hypomethylation of CD30 CpG islands with aberrant JunB expression drives CD30 induction in Hodgkin lymphoma and anaplastic large cell lymphoma, Laboratory Investigation,2008,88:48-57
[157]Kito H, Suzuki H, Ichikawa T, et al. Hypermethylation of the CD44 gene is associated with progression and metastasis of human prostate cancer. The Prostate,2001,49(2):110-115
[158]李丽娜. Methylation Status of CD44 Promoter Region in Primary Lung Cancer. "National Taiwan University Hospital,2005
[159]Gary A P, Zhou Y L, Linda A, et al. Inactivation of Misselected CD8 T Cells by CD8 Gene Methylation and Cell Death. Science,1999,28(4):1187-1191
[160]Hamerman J A, Page S T, Pullen A M. Distinct Methylation States of the CD8 Beta Gene in Peripheral T Cells and Intraeapithelial Lymphocytes [J]. The Journal of Immunology,1997, 159(3):1240-1246
[161]Kong L M, Liao C G, Chen L, et al. Promoter hypomethylation up-regulates CD 147 expression through increasing Spl binding and associates with poor prognosis in human hepatocellular carcinoma. Journal of cellular and molecular medicine,2011,15(6):1415-1428
[162]Parinaz A, Emmett O, Peggy H, et al. TOX Provides a Link Between Calcineurin Activation and CD8 Lineage Commitment. J. Exp. Med.,2004,12:1089-1099
[163]Maier H, Colbert J, Fitzsimmons D, et al. Activation of the Early B-Cell-Specific mb-1(Ig-α) Gene by Pax-5 Is Dependent on an Unmethylated Ets Binding Site, MOLECULAR AND CELLULAR BIOLOGY,2003, (3):1946-1960
[64]Lee P P, Fitzpatrick D R, Beard C, et al. A critical role for Dnmtl and DNA methylation in T cell development, function, and survival. Immunity,2001,15:763-774
[1]Randelli E. Buonocore F, Scapigliati G. Cell markers and determinants in fish immunology. Fish & Shellfish Immunology,2008,25:326-340
[2]徐胜威,斜带石斑鱼CD8α和C、D8β基因克隆及表达模式分析.中山大学硕士学位论文,2010
[3]Hu Q H, Pan Z M, Deen S. New alleles of chicken CD8 & and CD3d found in Chinese native and western breeds, Veterinary Immunology and Immunopathology 120,2007:223-233
[4]Natalie J. Davidson and Richard L B. Delineation of chicken thymocytes by CD3-TCR complex, CD4 and CD8 antigen expression reveals phylogenically conserved and novel thymocyte subsets,1992, (410):1175-1182
[5]LUHTALA M. Chicken CD4, CD8ab, and CD8aa T Cell Co-Receptor Molecules, Poultry Science,1998,77:1858-1873
[6]LARRY W T and LOUISE M. Evolutionary conservation of antigen recognition:The chicken T-cell receptor b chain, Proc.Natl. Acad. Sci,1990,87:7856-7860
[7]Louise G D, Sham V N and Elizabeth M D. The marsupial CD8 gene locus:Molecular cloning and expression analysis of the alpha and beta sequences in the gray short-tailed opossum (Monodelphis domestica) and the tammar wallaby(Macropus eugenii), Veterinary Immunology andImmunopathology,2009,129(1):14-27
[8]唐秀山,王磊,廖定为,等.三黄鸡CD8α/βcDNA克隆与表达及其多克隆抗体的制备.中国农业大学学报2007,12(5)：5-9
[9]Somamoto T, Yoshiura Y, Nakanishi T, et al. Molecular cloning and characterization of two types of CD8a from ginbuna crucian carp, Carassius auratus langsdorfii. Dev Comp Immunol 2005,29:693-702
[10]许峰,秦玉蓉,阴彦辉,等.湖羊myogenin重组基因表达及其亚细胞定位的研究,中国农学通报,2011,27(7)：309-313
[11]Sonja K, Nina K M, Beatrice S, et al. Characterization of duck leucocytes by monoclonal antibodies. Dev Comp Immunol,2005,29:733-748
[12]Liaw H J, Chen W R, Huang Y C, Genomic Organization of the Chicken CD8 Locus Reveals a Novel Family of Immunoreceptor Genes, J. Immunol,2007,178:3023-3030
[13]Sonal P,(?)vergard, A C and Nerland A H. CD8a and CD8b in Atlantic halibut, Hippoglossus hippoglossus:Cloning, characterization and gene expression during viral and bacterial infection, Fish & Shellfish Immunology,2008,25:570-580
[14]Maisey E, Toro-Ascuy D, Montero, R et al. Identification of CD3ε, CD4, CD8b splice variants of Atlantic salmon, Fish & Shellfish Immunology,2011,28:1-8
[15]Murphy P M. The molecular biology of leukocyte chemoattractant receptors. Annual Review of Immunology,1994,12:593-633
[16]Murphy P M. Molecular piracy of chemokine receptors by herpes viruses. Infectious Agents and Disease-Reviews Issues and Commentary,1994,3(2):137-154
[17]廖定为.鸭CD8α分子克隆与多克隆抗体制备及MHC Ⅰ(?)β2m的表达.北京：中国农业大学硕士学位论文,2007
[18]Marko L, Clive A, Tregaskes, e tal. Polymorphism of chicken CD8-alpha, but not CD8-beta, Immunogenetics,1997,46:396-401
[19]Gao G F, Tormo J, Gerth U C, et al. Crystal structure of the complex between human CD8α and HLA-A2. Nature,1997,387:630-634
[20]Tanabe M, Karaki S, Takiguelai M, et al. Antigen recognition by the T-cell receptor is enhanced by CD8 alpha-chain binding to the alpha 3 domain of MHC class I molecules, not by signaling via the cytoplasmic domain of CD8 alpha. Int Immunol,1992,4:147-152
[21]Shaw A S, Chalupny J, Whitney J A, et al. Short related sequences in the cytoplasmic domains of CD4 and CD8 mediate binding to the amino-terminal domain of the p561ck tyrosine protein kinase. Mol Cell Biol,1990,10:1853-1862
[22]周琦,王文.DNA水平白然选择作用的检测.动物学研究,2004,25(1)：73-80
[23]Yang Z. Inference of selection from multiple species alignments [J]. Curr Opin Genet Dev, 2002,12:688-694
[24]Yang Z, Bielawski J P. Statistical methods for detecting molecular adaptation [J].Trends Ecol Evol,2000,15(12):496-503
[25]Simona P, Laura Ga, Francesco B. Lymphocyte differentiation in sea bass thymus:CD4 and CD8-a gene expression studies, Fish & Shellfish. Immunology,2009,27:50-56
[26]Hansen J D, Zapata A G. Lymphocyte development in fish and amphibians. Immunol Rev, 1998,166:199-220
[27]Kioussis D and Ellmeier W. Chromatin and CD4, CD8A and CD8B gene expression during thymic differentiation. Nature Reviews Immunology,2002,2:909-919
[28]岳华,黄兴,杨发龙,等.荧光定量RT-PCR检测鸡CD4、CD8基因表达水平.畜牧兽医学报2008,39(6)：784-790
[29]Racanelli V and Rehermann B. The liver as an immunological organ. Hepatology,2006, 43(s1):54-62
[30]Salem M L, Diaz-Montero C M, E1-Naggar S A, et al. The TLR3 agonist poly (I:C) targets CD8+T-cells and augments their antigen-specific responses upon their adoptive transfer into naive recipient mice. Vaccine,2009,27:549-557
[31]Xu S W, Wu J Y, Hu K J, et al. Molecular cloning and expression of orange-spotted grouper(Epinephelus coioides) CD8a and CD8b genes, Fish& Shellfish Immunology,2011, 30:600-608
[32]Ciencewicki J, Brighton L, Wu W D, et al. Diesel exhaust enhances virus-and poly (I:C)-induced Toll-like receptor 3 expression and signaling in respiratory epithelial cells, Am J Physio! Lung Cell Mol Physiol,2006,290:1154-1163
[33]Reimer T, Brcic M, Schweizer M, et al. Poly (I:C) and LPS induce distinct IRF3 and NF-B signaling during type-I IFN and TNF responses in human macrophages, J. Leukoc.Biol,2008, 83:1249-1257
[34]Reaiche G Y. Characterization of the events involved in the resolution of acute duck hepatitis B virus infection, thesis of the university of Adelaide, south Australia,2008
[35]Gu C Q, Xie C Q, Hu X Y, et al. Cytokine gene expression in the livers of ducklings infected with duck hepatitis virus-1 JX strain. Poultry Science,2012,91:583-591
[36]陈志胜,王丙云,潘忠雄,等.鸭肝炎病毒诱导雏鸭细胞凋亡的研究,中国兽医学报,2003,23(02)：136-137
[37]Abdul-Careem, M F and Hunter B D. Cytokine gene expression patterns associated with immunization against Marek's disease in chickens. Vaccine,2007,25:424-432
[38]Ottenhoff T H and Mutis T. Role of cytoxic cells in the protective immunity against and immunopathology of intracellular infections. European Journal of Clinical Investigation.1995, 25:371-377
[39]郑玉姝,赵宏坤.崔治中.禽网状内皮组织增生病病毒感染SPF鸡对脾细胞中产生IFN-y的影响,农业生物技术学报,2007,15(1)：112-114
[40]Suetake H, Araki K, Akatsu K. et al. Genomic organization and expression of CD8a and CD8b genes in fugu Takifugu rubripes. Fish & Shellfish Immunology,2007,23:1107-1118
[41]Anwarul Islam M D. Adrian O Vladutiu M D and Theresa Donahue M T. CD8 Expression on B Cells in Chronic Lymphocytic Leukemia, Arch Pathol Lab Med,2000,124:1361-1363
[42]Giovanni Carulli M D, Alessandra Stacchini and Alessandra Marini M D. Aberrant Expression of CD8 in B-Cell Non-Hodgkin Lymphoma, Am J Clin Pathol,2009,132:186-190
[43]刘丽丽.家蚕LDLRD蛋白的表达分析及其亚细胞定位,浙江理工大学,硕士学位论文,2009
[44]王帅玉,盛清,吕正兵,等.家蚕Bm595的表达、组织分布及亚细胞定位.中国农业科学,2010,43(3)：648-654
[1]王洪梅,张利博,侯明海,等.牛Nramp1基因启动子的克隆及其活性分析.中国农业科学,2011,44(5)：1022-1028
[2]岳华,黄兴,杨发龙,等.荧光定量RT-PCR检测鸡CD4、CD8基因表达水平.畜牧兽医学报,2008,39(6)：784-790
[3]Mancebo E, Moreno-Pelayo M A, Mencia A, et al. Gly111Ser mutation in CD8A gene causing CD8 immunodeficiency is found in Spanish Gypsies. Molecular Immunology,2008,45: 479-484
[4]Kothlowa S, Mannesb N K, Schaerera B, et al. Characterization of duck leucocytes by monoclonal antibodies. Dev Comp Immunol,2005,29(5):733-748
[5]Feik N, Bilic I, Tinhofer J, et al. Functional and Molecular Analysis of the Double-Positive Stage-Specific CD8 Enhancer E8111 during Thymocyte Development. The Journal of Immunology,2005,174:1513-1524
[6]Landry D B, Engel J D and Sen R. Functional GATA-3 binding sites within murine CD8 alpha upstream regulatory sequences. J Exp Med.,2003,178(3):941-949
[7]Park J H.'Coreceptor tuning':cytokine signals transcriptionally tailor CD8 coreceptor expression to the self-specificity of the TCR. Nat Immunol,2007,8:1049-1059
[8]Bilic I. Negative regulation of CD8 expression via CD8 enhancer-mediated recruitment of the zinc finger protein MAZR. Nat Immunol,2006,7:392-400
[9]Jenkinson S R. Expression of the transcription factor cKrox in peripheral CD8 T cells reveals substantial postthymic plasticity in CD4-CD8 lineage differentiation. J Exp Med.2007,204: 267-272
[10]Hassana H, Sakaguchi S, Tenno M, et al. Cd8 enhancer E8I and Runx factors regulate CD8a expression in activated CD8+T cells.
[11]Frederick W. Alt Advances in Immunology,2011
[12]祁胜宾,双剑博,卢晓昭,等.GDDR基因启动子的克隆和报告基因载体构建.细胞与分子免疫学杂志,2011,27(2)：229-232
[13]MARTHA L B. Computational prediction of transcription factor binding site locations. Genome Biology,2003,5(1):201-212
[14]刘永峰,咎林森,赵栓平,等.牛GDF5基因启动子的克隆与序列分析.畜牧兽医学报,2010,41(4)：392-397
[15]LAGRANGE T, GAU VIN S, MACHE R, et al. S2F,a leaf specific transacting factor, binds to a novel cis-acting element and differentially activates the RPL21 gene. Plant Cell,1997 August,9(8):1469-1479
[16]Frith M C, Valen E, Krogh A. A code for transcription initiation in mammalian genomes. Genome Res,2008,18:1-12
[17]陈华,陈宏权,周倩倩,等.猪THRSP基因5'侧翼区序列转录调控活性的鉴定.畜牧兽医学报,2011,42(3)：329-334
[18]韩凤桐,林秀坤,刘娣,等.牛Sry启动子调控序列的鉴定.中国农业科学,2010,43(14)：18-26
[19]Gao M H and Kavathas P B. Functional importance of the cyclic AMP response element-like decamer motif in the CD8 alpha promoter. Immunol,1993,150(10):4376-4385
[20]余瑞元,王燕峰,徐长法.CREB研究进展.中国生物工程杂志,2003,13(1)：39-43
[21]Wen AY, Sakamoto K M, Miller L S. The role of the transcription factor CREB in immune function. Immunol,2010 Dec 1,185(11):6413-6419
[22]Landry D B, Engel J D and Sen R. Functional GATA-3 Binding Sites within Murine CD8a Upstream Regulatory Sequences. J. Exp. Med.,1993,178:941-949
[23]Winslow M M, Dayton T L, Verhaak R G, et al. Suppression of lung adenocarcinoma progression by Nkx2-1, Nature,2011,473:101-104
[24]程璐,王波.甲状腺转录因子NKx2.1的疾病研究进展.生命科学,2011,(8)：762-765
[25]金呈强,刘仿.转录因子GATA-1的研究进展.国际免疫学杂志,2009,32(01)：47-51
[26]冯洁,臧国庆,余永胜.转录因子AP-1在肝病中的作用.肝脏,2007,12(5)：418-419
[27]Hang M H, Chou C M, Hsieh Y C, et al. Identification of 5'-upstream region of pufferfish ribosomal protein 129 gene a strongconstitutive pmmoter to drive GFP expression in zebrafish. Biochem Biophys Res Commun,2004,314:249-258
[28]McCarroll S A, Li H and Bargmann C I. Identification of Transcriptional Regulatory Elements in Chemosensory Receptor Genes by Probabilistic Segmentation. Current Biology, 2005,15:347-352
[29]Cooper S J and Nathan D. Comprehensive analysis of transcriptional promoter structure and function in 1% of the human genome. Genome Res,2006,16:1-10
[30]Peterson M J and Morris J F. Human myeloid zinc finger gene MZF produces multiple transcript and encodes a SCAN box protein. Gene,2000,254(1-2):105-118
[1]张春燕,邹平.表观遗传学及其研究进展.四川生理科学杂志,2006,28(2)：72-74
[2]Yu Y, Zhang H M, Tian F, et al. Quantitative Evaluation of DNA Methylation Patterns for ALVE and TVB Genes in a Neoplastic Disease Susceptible and Resistant Chicken Model PLoS ONE,2008,3(3):1-10
[3]Luo J, Yu Y, Zhang H M, et al. Down-regulation of Promoter Methylation Level of CD4 gene after MDV Infection in MD-susception Chicken line. BioMed Central (BMC) Genetics,2010, (5):25-31
[4]刘振山,李齐发,张庆波,等.犏牛及其亲本JGF2基因mRNA表达水平、DNA甲基化状态差异分析.自然科学进展,2009,19(4)：380-385
[5]Li Q H, Li N, Hu X X, et al. Genome-Wide Mapping of DNA Methylation in Chicken. PLoS ONE,2011,6(5):1-7
[6]Yang C, Zhang M J, Niu W P, et al. Analysis of DNA Methylation in Various Swine Tissues. PLoS ONE,2011,6(1):1-9
[7]田艳苓.鸡微卫星标记、DNA甲基化差异和FSHβ变异及其与体重和产蛋性状的关系.硕十学位论文,山东农业大学,2011
[8]蒋曹德,邓昌彦,熊远著.猪个体DNA甲基化百分差异与胴体性状的关系.农业生物技术学报,2005,13(2)：179-185
[9]谭小方,黄天华.HBV基因经生殖细胞垂直传播与DNA甲基化研究发展.癌变畸变突变,2008,20(3)：247-248
[10]Pestano G A, Zhou Y L, Trimble L A, et al. Inactivation of Misselected CD8 T Cells by CD8 Gene Methylation and Cell Death. Science,1999,28(4):1187-1191
[11]Hamerman J A, Page S T, Pullen A M. Distinct Methylation States of the CD8 Beta Gene in Peripheral T Cells and Intraeapithelial Lymphocytes. The Journal of Immunology,1997, 159(3):1240-1246
[12]Chen C, Chen H, Hsiau T, et al. Technical advance:methylation target array for rapid analysis of CPG island hypermethylation in multiple issue genomes. Am Pathol,2003,163(1): 37-45
[13]Shi H, Yan P S, Chen C, et al. ExPressed CpG island sequence tag microarray for screening of DNA hypermethylaion and gene silencing in cancer cells. Cancer Res,2002,62: 3214-3220
[14]Lander E S, Linton L M, Birren B, et al. Initial sequencing and analysis of the human genome. Nature,2001,409:860-921
[15]Takai, D. and Peter Jones. Comprehensive analysis of CpG islands in human chromosomes 21 and 22. PNAS,2002,99 (6):3740-3745
[16]Kawasaki T, Nosho K, Ohnishi M, et al. IGFBP3 Promoter Methylation in Colorectal Cancer: Relationship with Microsatellite Instability, CpG Island Methylator Phenotype, and p53, Neoplasia.2007,9(12):1091-1098
[17]Lai J C, Cheng Y W, Goan Y G, et al. Promoter methylation of O6-methy]guanine-DNA-methyltransferase in lung cancer is regulated by p53, DNA Repair, 2008,7(8):1352-1363
[18]Torng P L, Lin C W, Chan M W Y, et al. Promoter methylation of IGFBP-3 and p53 expression in ovarian endometrioid carcinoma, Molecular Cancer 2009,:120 doi:10.1186/1476-4598-8-120
[19]董瑞,赵瑞,郑珊,等.胆道闭锁患儿外周血T细胞ITGAL基因启动子区甲基化状态及其mRNA表达,中国循证儿科杂志,2011,6(3)：220-224
[20]Jeong Y S, Yeo S, Park J S, et al. DNA methylation state is preserved in the sperm-derived pronucleus of the pig zygote. Int. J. Dev. Biol.2007,51:707-714
[21]Yu Y, Zhang H M, Byerly M S, et al. Alternative splicing variants and DNA methylation status of BDNF in inbred chicken lines. BRAIN RESEARCH,2009,1-10
[22]凌飞,李加琪,王翀,等.猪脂联素基因启动子区甲基化与其mRNA表达分析,遗 传,2009,31(10)：1013-1019
[23]刘振山,李齐发,张庆波,等,犏牛及其亲本IGF2基因mRNA表达水平、DNA甲基化状态差异分析,自然科学进展,2009,9(4)：380-385
[24]荣美洁,李兰,董文娟.崂山奶山羊乳腺中孕激素受体基因甲基化与基因表达关系的研究,青岛农业大学学报(自然科学版),2010,27(3)：186-190
[25]Fan X, Inda M M, Tunon T, etal. Improvement of the methylation specific PCR technical conditions for the detection of p16 promoter hypermethylation in small amounts of tumor DNA. Oncol Rep,2002,9(1):181-183
[26]Zilberman D. The human promoter methylome. Nat Genet,2007,39(4):442-443
[27]Schutte M, Hruban R H, Geradts J, et al. Abrogation of the Rb/pl6 tumor-suppressive pathway in virtually all pancreatic carcinomas. Cancer Res,1997,57(15):3126-3130
[28]Gonzalgo M L, Hayashida T, Bender C M, et al. The role of DNA methylation in expression of the p19/p16 locus in human bladder cancer cell lines. Cancer Res,1998,58(6):1245-1252
[29]Brandeis M, Frank D, Keshet I, et al. Spl elements protect a CpG island from de novo methylation. Nature,1994,371(6496):435-438
[30]Macleod D, Charlton J, Mullins J, et al. Spl sites in the mouse aprt gene promoter are required to prevent methylation of the CpG island. Genes Dev,1994,8(19):2282-2292
[31]Brenner C, Deplus R, Didelot C. Myc represses transcription through recruitment of DNA methyltransferase corepressor. EMBO J,2005,24(2):336-346
[32]Di Croce L, Raker VA, Corsaro M, et al. Methyltransferase recruitment and DNA hypermethylation of target promoters by an oncogenic transcription factor. Science,2002, 295(5557):1079-1082
[33]Wu L M, Zhang F, Zhou L, et al. Predictive value of CpG island methylator phenotype for tumor recurrence in hepatitis B virus associated hepatocellular carcinoma following liver transplantation. BMC Cancer,2010,10:399
[34]Ehrlich. M. DNA methylation in cancer:too much, but also too little. Oncogene,2002,21(35): 5400-5413
[35]孔令敏,CD147基因的转录调控机制及其表观遗传修饰,第四军医大学学位论文,2010
[36]EDEN A, GAUDET F, WAGHMARE A, et al. Chromosomal instability and tumors promoted by DNA hypomethylation. Science,2003,300(5618):455
[37]FLORL A R, STEINHOF C, MULLER M, et al. Coordinate hypermethylation at specific genes in prostate carcinoma precedes L1NE-1 hypomethylation. Br J Cancer,2004,91(5): 985-994
[38]FEINBERG A P, TYCKO B. The history of cancer epigenetics. Nat Rev Cancer,2004,4(2): 143-153
[39]徐青.鸡DNA甲基化组织特异性及亲本与子代甲基化差异性研究,北京：中国农业大学博十论文,2006
[2]Bernard A Boumsell L. The clusters of differentiation (CD) defined by the First International Workshop on human leucocyte differentiation antigens. Hum Immunol,1984,11 (1):1-10
[3]杨汉春.动物免疫学(第二版),北京：中国农业大学出版社,2003
[4]廖定为,唐秀山,蒋一男,等.北京鸭CD8α分子克隆与表达及其多克隆抗体制备,中国兽医杂志,2008,44(6)：5-7
[5]白家媛.樱桃谷北京鸭CD8α胞外区多肽的原核表达、抗体制备及初步应用,华中农业大学硕士学位论文,2010
[6]Sonja Kothlowa, Nina K. Mannesb, Beatrice Schaerera, et al. Characterization of duck leucocytes by monoclonal antibodies. Dev Comp Immunol,2005,29:733-748
[7]廖定为.鸭CD8α分子克隆与多克隆抗体制备及MHC I和β2m的表达,北京：中国农业大学学位论文,2007
[8]Dembic Z, Haas W, Zamoyska R et al. Transfection of the CD8 gene enhances T-cell recognition. Nature,1987,326:510-511
[9]Luhtala M. Chicken CD4, CD8αβ,CD8aa T cell coreceptor molecules. Poultry science.1998, 77:1858-1873
[10]Urner J M, Brodsky M H, Irving B A, et al. Interaction of the N-terminal region of tyrosine kinase p561ck with cytoplasmic domain of CD4 and CD8 is mediated by cysteine motifs. Cell, 1990,60(5):755-765
[11]Luhtala M. Avian CD4, CD8aa and CD8αβ T cell coreceptor molecules. Turku Finland. Annales Universitat&Turkuensis,1997,274:1-95
[12]李卫,白家媛,许媛媛,等.麻鸭和樱桃谷北京鸭的CD3ω、CD4、CD8a基因ORF克隆及序列分析.中国农业科学,2009,42(12)：4428-4434
[13]Z. LI, K. E. NESTOR, Y. M SAIF, et al. Cross-Reactive Anti-Chicken CD4 and CD8 Monoclonal Antibodies Suggest Polymorphism of the Turkey CD8a Molecule. Poultry Science,1999,78:1526-1531
[14]胡青海,焦新安,潘志明,等.中国部分地方品种鸡CD4和CD8a基因cDNA的克隆与序列分析,畜牧兽医学报,2006,37(3)：216-221
[15]Luhtala M, Tregaskes C A, Young J, et al. Polymorphism of chicken CD8-alpha, but not CD8-beta. Immunogenetics,1997,46:396-401
[16]孔令敏.CD147基因的转录调控机制及其表观遗传修饰,第四军医大学学位论文,2010
[17]Vaquerizas J M, Kummerfeld S K, Teichmann SA, et al. A census of human transcription factors:function, expression and evolution. Nat Rev Genet,2009,10(4):252-263
[18]章成,史冬燕,曾黎琼,等.真核生物转录调控的研究进展.云南农业大学学报,2007,22：164-176
[19]刘德培,查锡良,药立波.医学分子生物学,北京：人民卫生出版社,2006
[20]Dever T E. Gene-specific regulation by general translation factors. Cell,2002,108(4):545-56
[21]Emerson B M. Specificity of gene regulation. Cell,2002.109(3):267-270
[22]Hobert. Common logic of transcription factor and microRNA action. Trends Biochem Sci, 2004,29:462
[23]M. Ptashne, A. Gann. Genes and Signals (Cold Spring Harbor Laboratory, Cold Spring Harbor, NY,2002
[24]Grimson A, Farh K K, Johnston W K, et al. MicroRNA targeting specificity in mammals: determinants beyond seed pairing. Mol. Cell,2007,27:91
[25]Pal Saetrom, Bret S E Heale, Ola Snove J et al. Distance constraints between microRNA target sites dictates efficacy and cooperativity. Nucleic Acids Res,2007,35:23-33
[26]Buck M J, Lieb J D. A chromatin-mediated mechanism for specification of conditional transcription factor targets. Nat. Genet,2006,38:1446
[27]Martijn Kedde, Markus J. Strasser, Bijan Boldajipour, et al. RNA-Binding Protein Dndl Inhibits MicroRNA Access to Target mRNA. Cell,2007,131:1273
[28]Robins H, Li Y. Padgett R W, Predicting microRNA Targets with High Precision. Proc. Natl. Acad.Sci,2005.102:4006
[29]Vasudevan S. Tong. Y J, Steitz A. Switching from Repression to Activation:MicroRNAs Can Up-Regulate Translation. Science,2007,31(8):19-31
[30]Pillai R S, Bhattacharyya S N, Filipowicz W. Repression of protein synthesis by miRNAs: how many mechanisms? Trends Cell Biol,2007,17:118
[31]Gray S, Levine M. Transcriptional repression in development. Curr Cell Biol,1996,8:358
[32]Davidson E H, Genomic Regulatory Systems, Academic Press, San Diego, CA,2001
[33]Alon U, An Introduction to Systems Biology:Design Principles of Biological Circuits (Chapman & Hall/CRC), Boca Raton, FL,2006
[34]Johnston R J, Chang S Jr, Etchberger J F, et al. MicroRNAs acting in a double-negative feedback loop to control a neuronal cell fate decision. Proc. Natl. Acad. Sci,2005, 102:124-149
[35]Tsang J, Zhu J, Oudenaarden van A. MicroRNA-mediated feedback and feedforward loops are recurrent network motifs in mammals. Mol.Cell,2007,26:753
[36]Thomson J M, Michael Thomson, Parker Joel S, et al. Extensive post-transcriptional regulation of microRNAs and its implications for cancer. Genes Dev,2006,20:2202
[37]Lee E J, Baek M, Gusev Y, et al. Systematic evaluation of microRNA processing patterns in tissues, cell lines, and tumors. RNA,2007,14:35
[38]Kawahara Y, Zinshteyn B, Sethupathy P, et al. Redirection of silencing targets by adenosine-to-inosine editing of miRNAs. Science,2007,315:1137
[39]Wray G A, Hahn M W, Abouheif E, et al. The evolution of transcriptional regulation in eukaryotes. Mol. Biol Evol,2003,20:1377
[40]Ellmeier W, Sawada S and Littman D R. The regulation of CD4 and CD8 coreceptor gene expression during T cell development. Annu. Rev. Immunol,1999,17:523
[41]Hostert A, Tolaini M, Festenstein, R, et al. A CD8 genomic fragment that directs subset-specific expression of CD8 in transgenic mice. J. Immunol.1997,158:4270
[42]Zhang X L, Seong R, Piracha R, et al. Distinct stage-specific cis-active transcriptional mechanisms control expression of T cell coreceptor CD8 alpha at double-and single-positive stages of thymic development. Immunol,1998,161:2254
[43]Ellmeier W, Sunshine M J, Losos K, et al. Multiple developmental stage-specific enhancers regulate CD8 expression in developing thymocytes and in thymus-independent T cells. Immunity,1998,9:485
[44]Taniuchi I, Ellmeier W and Littman D R. The CD4/CD8 lineage choice:New insights into epigenetic regulation during T cell development. Adv. Immunol,2004,83:55
[45]Ktistaki E, Garefalaki A, Williams A, et al. CD8 locus nuclear dynamics during thymocyte development. Immunol,2010,184:56-86
[46]Ellmeier W, Sunshine M J, Maschek R, et al. Combined deletion of CD8 locus cis-regulatory elements affects initiation but not maintenance of CD8 expression. Immunity.2002,16:623
[47]Feik N, Bilic I, Tinhofer J, et al. Functional and molecular analysis of the double-positive stage-specific CD8 enhancer E8Ⅲ during thymocyte development. J. Immunol,2005,174: 1513
[48]Chi T H, Wan M, Zhao K, et al. Reciprocal regulation of CD4/CD8 expression by SWI/SNF-like BAF complexes. Nature,2002,418:195
[49]Bilic I, Koesters C, Unger B, et al. Negative regulation of CD8 expression via Cd8 enhancer-mediated recruitment of the zinc finger protein MAZR. Nat. Immunol,2006,7:392
[50]Lee P P, Fitzpatrick D R, Beard C, et al. A critical role for Dnmtl and DNA methylation in T cell development, function, and survival. Immunity,2001,15:763
[51]Ng S Y, Yoshida T and Georgopoulos K. Ikaros and chromatin regulation in early hematopoiesis. Curr. Opin. Immunol,2007,19:116
[52]Yasui Y, Miyano M, Cai S, et al. SATB1 targets chromatin remodelling to regulate genes over long distances. Nature,2002,419:641
[53]Nie H, Yao X, Maika S D, et al. SATB1 is required for CD8 coreceptor reversal. Mol. Immunol,2008,46:207
[54]Albu D I, Feng D, Bhattacharya D, etal. BCL11B is required for positive selection and survival of double-positive thymocytes. Exp. Med,2007,204:3003
[55]Trygve O Tollefsbol. Epigenetics Protocols. Totowa New Jersey:Humana Press,2004
[56]Esteller, M. Epigenetic gene silencing in cancer:the DNA hypermethylome. Hum. Mol. Genet,2007,16(1):50-59
[57]Lopez-Serra L and Esteller M. Proteins that bind methylated DNA and human cancer:reading the wrong words. Br. J. Cancer,2008,98:1881-1885
[58]Kuroda A, Rauch A T, Todorov I, et al. Insulin gene expression is regulated by DNA methylation. PLoS ONE,2009,4:95
[59]Thomson J P, Skene P J, Selfridge J, et al. CpG islands influence chromatin structure via the CpG-binding protein Cfpl. Nature,2010,464:1082-1086
[60]Comb M, Goodman H M. CpG methylation inhibits proenkephalin gene expression and binding of the transcription factor AP-2. Nucleic Acids Res,1990,18(13):3975-3982
[61]Prendergast G C, Lawe D, Ziff E B. Association of Myn, the murine homolog of max, with c-Myc stimulates methylation-sensitive DNA binding and ras cotransformation. Cell,1991 May 3,65(3):395-407
[62]Mancini D N, Rodenhiser D I, Ainsworth P J, et al. CpG methylation within the 5'regulatory region of the BRCA1 gene is tumor specific and includes a putative CREB binding site. Oncogene,1998,16(9):1161-1169
[63]Mancini D N, Singh S M, Archer T K, et al. Site-specific DNA methylation in the neurofibromatosis (NF1) promoter interferes with binding of CREB and SP1 transcription factors. Oncogene,1999,18(28):4108-4119
[64]Campanero M R, Armstrong M I, Flemington E K. CpG methylation as a mechanism for the regulation of E2F activity. Proc Natl Acad Sci USA,2000,97(12):6481-6486
[65]Robertson K D, Ait-Si-Ali S, Yokochi T, et al. DNMT1 forms a complex with Rb, E2F1 and HDAC1 and represses transcription from E2F-responsive promoters. Nat Genet,2000,25(3): 338-342
[66]Prokhortchouk A, Hendrich B, Jorgensen H, et al. The pi20 catenin partner Kaiso is a DNA methylation-dependent transcriptional repressor. Genes Dev,2001,15(13):1613-1618
[67]Prokhortchouk E, Hendrich B. Methyl-CpG binding proteins and cancer:are MeCpGs more important than MBDs? Oncogene,2002,21(35):5394-5399
[68]Wolffe A P. Packaging principle:how DNA methylation and histone acetylation control the transcriptional activity of chromatin. Exp Zool.1998,282(1-2):239-244
[69]Kundu T K, Rao M R. CpG islands in chromatin organization and gene expression. J Biochem,1999,125(2):217-222
[70]Nakao M. Epigenetics:interaction of DNA methylation and chromatin. Gene,2001,278(1-2): 25-31
[71]Jiang C D, Deng C Y, Xiong Y Z. Patterns of cytosine methylation in parental lines and their hybrids of Large White and Meishan reciprocal crosses. Agricultural Science in China,2004, 3(1):57-63
[72]Xu Q, Zhang Y, Sun D, et al. Analysis on DNA methylation of various tissues in chicken [J]. Anim Biotechnol,2007,18(4):231-241
[73]徐青.鸡DNA甲基化组织特异性及亲本与子代甲基化差异性研究,北京：中国农业大学博十学位论文,2006
[74]林莉.体细胞克隆牛功能基因DNA甲基化及其表达差异,北京：中国农业大学博士学位论文,2007
[75]Cockett N E, Shay T L, Green R D et al. Rapid communications Taq1 restriction fragment length polymorphism in the bovine calpastatin gene. Anim Sci,1995,73(12):3790
[76]Timothy A H, Robert W R and Jennifer A M G. Construction and evolution ofimprinted loci in mammals. Trends in Genetics,2007,23(9):440-448
[77]张立岭,林花,杨丽君.蒙古羊胸椎数的亲本印记遗传研究.内蒙古农业大学学报,2000,21(2)：1-6
[78]Noyer J L, Causse S, Tomekpe K, et al. A new image of plantain diversity assessed by SSR, AFLP and MSAP markers. Genetica,2005,124(1):61-69
[79]洪柳,邓秀新.应用MASP技术对脐橙品种进行DNA甲基化分析.中国农业科学,2005,38(11)：2301-2307
[80]W ilson A S, Power B E and Molloy P L. DNA hypomethylation and human diseases. Biochim. Biophys. Acta,2007,1775:138-162
[81]Ito Y, Koessler T, Ibrahim A E K, et al. Somatically acquired hypomethylation of IGF2 in breast and colorectal cancer. Hum. Mol. Genet,2008,17:2633-2643
[82]Lujambio, A. Ropero S, Ballestar E, et al. Genetic unmasking of an epigenetically silenced microRNA in human cancer cells. Cancer Res,2007,67:1424-1429
[83]Lujambio A, Calin G A, Villanueva A, et al. A microRNA DNA methylation signature for human cancer metastasis. Proc. Natl. Acad. Sci,2008, USA 105:13556-13561
[84]Chahrour M, Jung SY, Shaw C, et al. MeCP2, a key contributor to neurological disease, activates and represses transcription. Science,2008,320:1224-1229
[85]Urdinguio RG, Sanchez-Mut J V, Esteller M. Epigenetic mechanisms in neurological diseases: genes, syndromes, and therapies. Lancet Neurol.2009,8:1056-1072
[86]Robertson K D. DNA methylation and human disease. Nat. Rev. Genet,2005,6:597-610
[87]Jin B, Li Q, Zhang L, et al. DNA methyl transferase 3B (DNMT3B) mutations in 1CF syndrome lead to altered epigenetic modifications and aberrant expression of genes regulating development, neurogenesis and immune function. Hum. Mol. Genet,2008,17:690-709
[88]Pan W, Zhu S, Yuan M. et al. MicroRNA-21 and microRNA-148a contribute to DNA hypomethylation in lupus CD4+T cells by directly and indirectly targeting DNA methyl transferase. Immunol,2010,184:6773-6781
[89]Herman J q, Graff J R, Myohanen S, et al. Methlation 2 Specific PCR:A novel PCR assay for methylation status of CPG islands. Proc Natl Acad Sci, USA,1996,93(18):9821-9826
[90]张云,辛海明,刘泽军,等.p53凋亡刺激蛋白基因5'端非编码区CpG岛高甲基化与其mRNA表达的改变.第三军医大学学报,2005,27(21)：2103-2106
[91]Herman J G, Baylin S B. Methylation-specific PCR Current Protocols in Human Genetics, 1998,10(6):1-10
[92]凌飞.猪Myll与adiponectin基因启动子克隆及其表达调控研究,华南农业大学学位论文,2008
[93]肖正中.猪基因组甲基化位点的克隆及Lyn基因转录调控分析,华南农业大学学位论文,2009
[94]刘晓瑛,李金龙,傅业全,等.鸡马立克氏病肾肿瘤p15基因的甲基化特异性PCR检测,中国兽医科学,2010,40(01)：61-64
[95]Frommer M, MeDonald L E, Millar D S, et al., A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands. Proc Natl Acad Sci,1992,89(5):1827-1831
[96]林莉.体细胞克隆牛功能基因DNA甲基化及其表达差异,中国农业大学学位论文,2007
[97]荣美洁,李兰,董文娟,等.崂山奶山羊乳腺中孕激素受体基因甲基化与基因表达关系的研究,青岛农业大学学报(自然科学版)2010,27(3)：186-190
[98]白同,杨斌,娄诚,等.APC和CDKN2A基因甲基化定量分析对肝细胞癌的诊断价值,世界华人消化杂志,2009,17(29)：3001-3007
[99]周少贞,李相辉,张玉祥.EGFR基因启动子区甲基化状态分析,中国生物化学与分子生物学报,2010,26(6)：568-574
[100]SuY, Dodson M V, Li X B. The effects of dietary betaine supplementation on fatty liver performance, serum parameters, histological changes, methylation status and the mRNA expression level of Spotl4a in Landes goose fatty liver. Comparative Biochemistry and Physiology,2009,154:308-314
[101]赵贵森,郑海燕,莫耀南,等.一种用于DNA甲基化分析的改进型亚硫酸氢盐转化法,中国生物化学与分子生物学报,2007,23(10)：876-880
[102]张祖萍,脑胶质瘤的表观遗传学研究.中南人学博十学位论文,2009
[103]Xiong Z and Laird P W. COBRA:a sensitive and quantitative DNA methylation assay. Nucleic Acids Res,1997,25(12):2532-2534
[104]Brena R M, Auer H, Komacker K, et al. Accurate quantifcation of DNA methylation using combined bisulfite restricfion anlalysis coupled with the Agilent 2100 Bioanalyzer platform. Nucleic Acids Ras,2006,34(3):17
[105]Eads C A, Danenberg K D, Kawakami K, et al. MethyLight:a high-throughput assay to measure DNA methylation. Nucleic Acids Res,2000,28(8):32
[106]Wittwer C T, Gudrun H R, Cameron N G, et al. High-resolution genotyping by amplicon melting analysis using LCGreen. Clin Chem,2003,49(6):853-860
[107]李宏伟,李慎,梁平,等.焦磷酸测序检测RARβ2基因启动子甲基化方法的建立,第四军医大学学报,2009,30(14)：1285-1288
[108]Ying Y, Zhang H M, Tian F, et al. Quantitative Evaluation of DNA Methylation Patterns for ALVE and TVB Genes in a Neoplastic Disease Susceptible and Resistant Chicken Model. PLoS ONE,2008,3(3):1-10
[109]Luo J, Ying Y, Zhang H M, et al. Down-regulation of Promoter Methylation Level of CD4 gene after MDV Infection in MD-susception Chicken line. BioMed Central (BMC) Genetics, 2010, (5):25-31
[110]Kuo K C. McCune R A, Gehrke C W, et al. Quantitative reversed-phase high performance liquid chromatographic determination of major and modified deoxyribonucleosides in DNA, Nucleic Acids Res,1980,24; 8(20):4763-4776
[111]Mario F F, Esther U L, Borja D, et al. High-performance capillary electrophoretic method for the quantification of 5-methyl 2'-deoxycytidine in genomic DNA:Application to plant, animal and human cancer tissues. Electrophoresis,2002,23(11):1677-1681
[112]邓大君,邓国仁,吕有勇,等.变性高效液相色谱法检测CpG岛胞嘧啶甲基化.中华医学杂志,2001,80(2)：158-161
[113]Ramsahoye B H. Measurement of genome wide DNA methylation by eversed-phase high-performance liquid chromatography. Methods,2002,27:156-161
[114]蔡鑫泽,乔莹,都姝妍,等.反相高效液相色谱法测定人乳腺癌MCF7细胞中基因组DNA甲基化水平,中国医科大学学报,39(11)：898-903
[115]张俊杰,张立坚,刘春安,等.组织中全基因组DNA甲基化的液相色谱-串联质谱分析,质谱,2010,31(6)：326-330
[116]Liguo S, James S R, Kazim L, et al. Specific Method for the Determination of Genomic DNA Methylation by Liquid Chromatography-Electrospray Ionization Tandem Mass Spectrometry, Anal. Chem,2005,77:504-510
[117]Kelly M, Armstrong E N, Berminghaml S A, et al. Global DNA methylation measurement by HPLC using low amounts of DNA. Biotechnol. J,2011,6:113-117
[118]Jason W J, Harding K, David H B, et al. HPLC analysis of plant DNA methylation:a study of critical methodological factors. Plant Physiology and Biochemistry,2005,43:844-853
[119]梁秋菊,刘丽娜,彭健,等.猪血液和肌肉组织DNA甲基化含量的测定.中国农业科学.2007,40(8)：1774-1779
[120]尹慧,黄代新,翟仙敦,等.HPLC法检测人外周血5m C含量及其与年龄相关性研究,中国法医学杂志,2007,22(1)：8-11
[121]陈英.荣昌猪DNA甲基化水平的差异分析,西南大学学位论文,2009
[122]张志勇,李春宏,仇小强,等.广西长寿地区人群白细胞DNA总体甲基化水平研究,中国老年学杂志,2009,29：1513-1516
[123]宗凯,刘国庆,曹树青,等.日粮蛋氨酸和赖氨酸水平对肉鸡生长性能及肌肉和肝脏组织DNA甲基化含量的影响,粮食与饲料工业,2010,2：33-37
[124]万亚琴.DNA甲基化与肉牛杂种优势关系的初步研究,两南大学硕士学位论文,2008
[125]蒋曹德,邓昌彦,熊远著,等.DNA甲基化差异对猪生长性状的影响,畜牧兽医学报,2005,36(2)：105-110
[126]班谦,家鸡胚胎早期发育过程中DNA甲基化的MSAP分析,石河子大学,2009
[127]肖正中,刘小红,王翀,等.长白猪×蓝塘猪及其杂种基因组DNA甲基化分析,畜牧兽医学报,2011,42(5)：613-620
[128]唐韶青,张沅,徐青,等.不同动物部分组织基因组甲基化程度的差异分析,农业生物技术学报,2006,14(4)：507～510
[129]Xu Q, Zhang Y, Sun D, et al. Analysis on DNA methylation of various tissues in chicken. Anim Biotechnol,2007,18(4):231-241
[130]Chun Y, Zhang M J, Niu W P, et al. Analysis of DNA Methylation in Various Swine Tissues. PLoS ONE,2011,6(1):162
[131]徐青,张沅,孙东晓,等.应用MSAP方法检测鸡不同组织基因组的甲基化状态,遗传,2011,33(6)：620-626
[132]Tibor Rauch, Zunde Wang, Xinmin Zhang, et al. Homeobox gene methylation in lung cancer studied by genome-wide analysis with a microarray-based methylated CpG island recovery assay. Proc Natl Acad Sci U S A,2007,104(13):5527-5555
[133]Michael W, Jonathan J D, David W, et al. Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cells. Nat Genet,2005,37(8):853-862
[134]Zhang X Y, Yazaki J S, Sundaresan A, et al. Genome-wide high-resolution mapping and functional analysis of DNA methylation in arabidopsis. Cell,2006,126(6):1189-1201
[135]Lister R, Malley R C, Tonti-Filippini J, et al. Highly integrated single-base resolution maps of the epigenome in Arabidopsis. Cell,2008,133(3):523-536
[136]Yoshinao R, Yukako I, Fumiaki S, et al. Genome-wide analysis of aberrant methylation in human breast cancer cells using methyl-DNA immunoprecipitation combined with high-throughput sequencing. BMC Genomics,2010,11:137
[137]Li Q H, Li N, Hu X X, et al. Genome-Wide Mapping of DNA Methylation in Chicken. PLoS ONE,2011,6(5):1942
[138]Benjamin A F, Webste D R, Lee J H, et al. Direct detection of DNA methylation during single-molecule, real-time sequencing. Nature Methods 7,2010,1:461-465
[139]熊启香,熊莉娟.乙型肝炎病毒感染与肝细胞癌DNA甲基化研究进展,临床肝胆病杂志,2011,27(8)：881-884
[140]Ji C Z, Zong T Y, Jun L, et al. Persistent infection of hepatitis B virus is involved in high rate of p 16 methylation in hepatocelluarcarcinoma. Mol Carcinog,2006,45(7):530-536.
[141]Shim Y H, Yoon G S, Choi H J, et al. p16 Hypermethylation in theearly stage of hepatitis B virus -associated hepatocarcinogenesis. Cancer Lett,2003,190(2):213-219.
[142]Zhong S, Tang M W, Yeo W, et al. Intensive hypermethylation of theCpG island of Ras association domain family 1A in hepatit is B virus-associated hepatocellular carcinomas. Clin Cancer Res,2003,9(9):3376-3382.
[143]Zhong S, Tang M W, Yeo W, et al. S ilencing of G STP1 gene by CpG island DNA hypermethylation in HBV-associated hepatocellular carinomas. Clin Cancer Res,2002,8(4): 1087-1092.
[144]Yang B, Guo M, Herman J G, et al. Aberrant promoter methylatio nprofiles of tumor suppressor genes in hepatocellular carcinoma. Am J Pathol,2003,163(3):1101-1107.
[145]Wei Y, Van N, Prigent S, et al. Altered expression of E-cadherin in hepatocellular carcinoma:correlations with geneticalterations, beta-catenin expression, and clinical features. Hepatology,2002,36(3):692-701.
[146]郭朝阳.慢加急性肝衰竭患者外周血肿瘤坏死因子-α基因启动子甲基化状态的研究,山东大学硕士学位论文,2010
[147]于淑霞.IL-10在慢性乙型肝炎和慢加急性肝衰竭患者中启动子甲基化研究,山东大学硕士学位论文,2010
[148]李凤彩.慢加急性重型乙型病毒性肝炎患者血清IFN-γ水平及其启动子甲基化状态研究,山东大学硕士学位论文,2010
[149]张海元,云鹏.肝癌细胞系中Runx3基因表达及启动子区异常甲基化分析.长江大学学报(自然科学版),2009,36(1)：1-3
[150]Hammad H, Shinya S, Mari T, et al. Cd8 enhancer E8I and Runx factors regulate CD8a expression in activated CD8+T cells. PNAS,2011,108:18330-18335
[151]Flanagan B F, Wotton D, Tuck-Wah S, et al. DNase hypersensitivity and methylation of the human CD3G and D genes during T-cell development. Immunogenetics,1990,31(1):13-20
[152]Taylor K H, Liu.J. Guo J, et al. Promoter DNA methylation of CD10 in lymphoid malignancies. Leukemia,2006,20:1910-1912
[153]Guillermo G, Daniel J, Smith T L, et al. DNA Methylation of Multiple Promoter-associated CpG Islands in Adult Acute Lymphocytic Leukemia. Clin Cancer Res,2002,8:2217-2224.
[154]Schwab J and Illges H. Regulation of CD21 expression by DNA methylation and histone deacetylation. International Immunology,2001,13(5):705-710
[155]张勤,王金玉,主编.动物遗传育种研究最新进展论文集,2011
[156]Mariko W, Ogawal Y, Itoh K, et al. Hypomethylation of CD30 CpG islands with aberrant JunB expression drives CD30 induction in Hodgkin lymphoma and anaplastic large cell lymphoma, Laboratory Investigation,2008,88:48-57
[157]Kito H, Suzuki H, Ichikawa T, et al. Hypermethylation of the CD44 gene is associated with progression and metastasis of human prostate cancer. The Prostate,2001,49(2):110-115
[158]李丽娜. Methylation Status of CD44 Promoter Region in Primary Lung Cancer. "National Taiwan University Hospital,2005
[159]Gary A P, Zhou Y L, Linda A, et al. Inactivation of Misselected CD8 T Cells by CD8 Gene Methylation and Cell Death. Science,1999,28(4):1187-1191
[160]Hamerman J A, Page S T, Pullen A M. Distinct Methylation States of the CD8 Beta Gene in Peripheral T Cells and Intraeapithelial Lymphocytes [J]. The Journal of Immunology,1997, 159(3):1240-1246
[161]Kong L M, Liao C G, Chen L, et al. Promoter hypomethylation up-regulates CD 147 expression through increasing Spl binding and associates with poor prognosis in human hepatocellular carcinoma. Journal of cellular and molecular medicine,2011,15(6):1415-1428
[162]Parinaz A, Emmett O, Peggy H, et al. TOX Provides a Link Between Calcineurin Activation and CD8 Lineage Commitment. J. Exp. Med.,2004,12:1089-1099
[163]Maier H, Colbert J, Fitzsimmons D, et al. Activation of the Early B-Cell-Specific mb-1(Ig-α) Gene by Pax-5 Is Dependent on an Unmethylated Ets Binding Site, MOLECULAR AND CELLULAR BIOLOGY,2003, (3):1946-1960
[64]Lee P P, Fitzpatrick D R, Beard C, et al. A critical role for Dnmtl and DNA methylation in T cell development, function, and survival. Immunity,2001,15:763-774
[1]Randelli E. Buonocore F, Scapigliati G. Cell markers and determinants in fish immunology. Fish & Shellfish Immunology,2008,25:326-340
[2]徐胜威,斜带石斑鱼CD8α和C、D8β基因克隆及表达模式分析.中山大学硕士学位论文,2010
[3]Hu Q H, Pan Z M, Deen S. New alleles of chicken CD8 & and CD3d found in Chinese native and western breeds, Veterinary Immunology and Immunopathology 120,2007:223-233
[4]Natalie J. Davidson and Richard L B. Delineation of chicken thymocytes by CD3-TCR complex, CD4 and CD8 antigen expression reveals phylogenically conserved and novel thymocyte subsets,1992, (410):1175-1182
[5]LUHTALA M. Chicken CD4, CD8ab, and CD8aa T Cell Co-Receptor Molecules, Poultry Science,1998,77:1858-1873
[6]LARRY W T and LOUISE M. Evolutionary conservation of antigen recognition:The chicken T-cell receptor b chain, Proc.Natl. Acad. Sci,1990,87:7856-7860
[7]Louise G D, Sham V N and Elizabeth M D. The marsupial CD8 gene locus:Molecular cloning and expression analysis of the alpha and beta sequences in the gray short-tailed opossum (Monodelphis domestica) and the tammar wallaby(Macropus eugenii), Veterinary Immunology andImmunopathology,2009,129(1):14-27
[8]唐秀山,王磊,廖定为,等.三黄鸡CD8α/βcDNA克隆与表达及其多克隆抗体的制备.中国农业大学学报2007,12(5)：5-9
[9]Somamoto T, Yoshiura Y, Nakanishi T, et al. Molecular cloning and characterization of two types of CD8a from ginbuna crucian carp, Carassius auratus langsdorfii. Dev Comp Immunol 2005,29:693-702
[10]许峰,秦玉蓉,阴彦辉,等.湖羊myogenin重组基因表达及其亚细胞定位的研究,中国农学通报,2011,27(7)：309-313
[11]Sonja K, Nina K M, Beatrice S, et al. Characterization of duck leucocytes by monoclonal antibodies. Dev Comp Immunol,2005,29:733-748
[12]Liaw H J, Chen W R, Huang Y C, Genomic Organization of the Chicken CD8 Locus Reveals a Novel Family of Immunoreceptor Genes, J. Immunol,2007,178:3023-3030
[13]Sonal P,(?)vergard, A C and Nerland A H. CD8a and CD8b in Atlantic halibut, Hippoglossus hippoglossus:Cloning, characterization and gene expression during viral and bacterial infection, Fish & Shellfish Immunology,2008,25:570-580
[14]Maisey E, Toro-Ascuy D, Montero, R et al. Identification of CD3ε, CD4, CD8b splice variants of Atlantic salmon, Fish & Shellfish Immunology,2011,28:1-8
[15]Murphy P M. The molecular biology of leukocyte chemoattractant receptors. Annual Review of Immunology,1994,12:593-633
[16]Murphy P M. Molecular piracy of chemokine receptors by herpes viruses. Infectious Agents and Disease-Reviews Issues and Commentary,1994,3(2):137-154
[17]廖定为.鸭CD8α分子克隆与多克隆抗体制备及MHC Ⅰ(?)β2m的表达.北京：中国农业大学硕士学位论文,2007
[18]Marko L, Clive A, Tregaskes, e tal. Polymorphism of chicken CD8-alpha, but not CD8-beta, Immunogenetics,1997,46:396-401
[19]Gao G F, Tormo J, Gerth U C, et al. Crystal structure of the complex between human CD8α and HLA-A2. Nature,1997,387:630-634
[20]Tanabe M, Karaki S, Takiguelai M, et al. Antigen recognition by the T-cell receptor is enhanced by CD8 alpha-chain binding to the alpha 3 domain of MHC class I molecules, not by signaling via the cytoplasmic domain of CD8 alpha. Int Immunol,1992,4:147-152
[21]Shaw A S, Chalupny J, Whitney J A, et al. Short related sequences in the cytoplasmic domains of CD4 and CD8 mediate binding to the amino-terminal domain of the p561ck tyrosine protein kinase. Mol Cell Biol,1990,10:1853-1862
[22]周琦,王文.DNA水平白然选择作用的检测.动物学研究,2004,25(1)：73-80
[23]Yang Z. Inference of selection from multiple species alignments [J]. Curr Opin Genet Dev, 2002,12:688-694
[24]Yang Z, Bielawski J P. Statistical methods for detecting molecular adaptation [J].Trends Ecol Evol,2000,15(12):496-503
[25]Simona P, Laura Ga, Francesco B. Lymphocyte differentiation in sea bass thymus:CD4 and CD8-a gene expression studies, Fish & Shellfish. Immunology,2009,27:50-56
[26]Hansen J D, Zapata A G. Lymphocyte development in fish and amphibians. Immunol Rev, 1998,166:199-220
[27]Kioussis D and Ellmeier W. Chromatin and CD4, CD8A and CD8B gene expression during thymic differentiation. Nature Reviews Immunology,2002,2:909-919
[28]岳华,黄兴,杨发龙,等.荧光定量RT-PCR检测鸡CD4、CD8基因表达水平.畜牧兽医学报2008,39(6)：784-790
[29]Racanelli V and Rehermann B. The liver as an immunological organ. Hepatology,2006, 43(s1):54-62
[30]Salem M L, Diaz-Montero C M, E1-Naggar S A, et al. The TLR3 agonist poly (I:C) targets CD8+T-cells and augments their antigen-specific responses upon their adoptive transfer into naive recipient mice. Vaccine,2009,27:549-557
[31]Xu S W, Wu J Y, Hu K J, et al. Molecular cloning and expression of orange-spotted grouper(Epinephelus coioides) CD8a and CD8b genes, Fish& Shellfish Immunology,2011, 30:600-608
[32]Ciencewicki J, Brighton L, Wu W D, et al. Diesel exhaust enhances virus-and poly (I:C)-induced Toll-like receptor 3 expression and signaling in respiratory epithelial cells, Am J Physio! Lung Cell Mol Physiol,2006,290:1154-1163
[33]Reimer T, Brcic M, Schweizer M, et al. Poly (I:C) and LPS induce distinct IRF3 and NF-B signaling during type-I IFN and TNF responses in human macrophages, J. Leukoc.Biol,2008, 83:1249-1257
[34]Reaiche G Y. Characterization of the events involved in the resolution of acute duck hepatitis B virus infection, thesis of the university of Adelaide, south Australia,2008
[35]Gu C Q, Xie C Q, Hu X Y, et al. Cytokine gene expression in the livers of ducklings infected with duck hepatitis virus-1 JX strain. Poultry Science,2012,91:583-591
[36]陈志胜,王丙云,潘忠雄,等.鸭肝炎病毒诱导雏鸭细胞凋亡的研究,中国兽医学报,2003,23(02)：136-137
[37]Abdul-Careem, M F and Hunter B D. Cytokine gene expression patterns associated with immunization against Marek's disease in chickens. Vaccine,2007,25:424-432
[38]Ottenhoff T H and Mutis T. Role of cytoxic cells in the protective immunity against and immunopathology of intracellular infections. European Journal of Clinical Investigation.1995, 25:371-377
[39]郑玉姝,赵宏坤.崔治中.禽网状内皮组织增生病病毒感染SPF鸡对脾细胞中产生IFN-y的影响,农业生物技术学报,2007,15(1)：112-114
[40]Suetake H, Araki K, Akatsu K. et al. Genomic organization and expression of CD8a and CD8b genes in fugu Takifugu rubripes. Fish & Shellfish Immunology,2007,23:1107-1118
[41]Anwarul Islam M D. Adrian O Vladutiu M D and Theresa Donahue M T. CD8 Expression on B Cells in Chronic Lymphocytic Leukemia, Arch Pathol Lab Med,2000,124:1361-1363
[42]Giovanni Carulli M D, Alessandra Stacchini and Alessandra Marini M D. Aberrant Expression of CD8 in B-Cell Non-Hodgkin Lymphoma, Am J Clin Pathol,2009,132:186-190
[43]刘丽丽.家蚕LDLRD蛋白的表达分析及其亚细胞定位,浙江理工大学,硕士学位论文,2009
[44]王帅玉,盛清,吕正兵,等.家蚕Bm595的表达、组织分布及亚细胞定位.中国农业科学,2010,43(3)：648-654
[1]王洪梅,张利博,侯明海,等.牛Nramp1基因启动子的克隆及其活性分析.中国农业科学,2011,44(5)：1022-1028
[2]岳华,黄兴,杨发龙,等.荧光定量RT-PCR检测鸡CD4、CD8基因表达水平.畜牧兽医学报,2008,39(6)：784-790
[3]Mancebo E, Moreno-Pelayo M A, Mencia A, et al. Gly111Ser mutation in CD8A gene causing CD8 immunodeficiency is found in Spanish Gypsies. Molecular Immunology,2008,45: 479-484
[4]Kothlowa S, Mannesb N K, Schaerera B, et al. Characterization of duck leucocytes by monoclonal antibodies. Dev Comp Immunol,2005,29(5):733-748
[5]Feik N, Bilic I, Tinhofer J, et al. Functional and Molecular Analysis of the Double-Positive Stage-Specific CD8 Enhancer E8111 during Thymocyte Development. The Journal of Immunology,2005,174:1513-1524
[6]Landry D B, Engel J D and Sen R. Functional GATA-3 binding sites within murine CD8 alpha upstream regulatory sequences. J Exp Med.,2003,178(3):941-949
[7]Park J H.'Coreceptor tuning':cytokine signals transcriptionally tailor CD8 coreceptor expression to the self-specificity of the TCR. Nat Immunol,2007,8:1049-1059
[8]Bilic I. Negative regulation of CD8 expression via CD8 enhancer-mediated recruitment of the zinc finger protein MAZR. Nat Immunol,2006,7:392-400
[9]Jenkinson S R. Expression of the transcription factor cKrox in peripheral CD8 T cells reveals substantial postthymic plasticity in CD4-CD8 lineage differentiation. J Exp Med.2007,204: 267-272
[10]Hassana H, Sakaguchi S, Tenno M, et al. Cd8 enhancer E8I and Runx factors regulate CD8a expression in activated CD8+T cells.
[11]Frederick W. Alt Advances in Immunology,2011
[12]祁胜宾,双剑博,卢晓昭,等.GDDR基因启动子的克隆和报告基因载体构建.细胞与分子免疫学杂志,2011,27(2)：229-232
[13]MARTHA L B. Computational prediction of transcription factor binding site locations. Genome Biology,2003,5(1):201-212
[14]刘永峰,咎林森,赵栓平,等.牛GDF5基因启动子的克隆与序列分析.畜牧兽医学报,2010,41(4)：392-397
[15]LAGRANGE T, GAU VIN S, MACHE R, et al. S2F,a leaf specific transacting factor, binds to a novel cis-acting element and differentially activates the RPL21 gene. Plant Cell,1997 August,9(8):1469-1479
[16]Frith M C, Valen E, Krogh A. A code for transcription initiation in mammalian genomes. Genome Res,2008,18:1-12
[17]陈华,陈宏权,周倩倩,等.猪THRSP基因5'侧翼区序列转录调控活性的鉴定.畜牧兽医学报,2011,42(3)：329-334
[18]韩凤桐,林秀坤,刘娣,等.牛Sry启动子调控序列的鉴定.中国农业科学,2010,43(14)：18-26
[19]Gao M H and Kavathas P B. Functional importance of the cyclic AMP response element-like decamer motif in the CD8 alpha promoter. Immunol,1993,150(10):4376-4385
[20]余瑞元,王燕峰,徐长法.CREB研究进展.中国生物工程杂志,2003,13(1)：39-43
[21]Wen AY, Sakamoto K M, Miller L S. The role of the transcription factor CREB in immune function. Immunol,2010 Dec 1,185(11):6413-6419
[22]Landry D B, Engel J D and Sen R. Functional GATA-3 Binding Sites within Murine CD8a Upstream Regulatory Sequences. J. Exp. Med.,1993,178:941-949
[23]Winslow M M, Dayton T L, Verhaak R G, et al. Suppression of lung adenocarcinoma progression by Nkx2-1, Nature,2011,473:101-104
[24]程璐,王波.甲状腺转录因子NKx2.1的疾病研究进展.生命科学,2011,(8)：762-765
[25]金呈强,刘仿.转录因子GATA-1的研究进展.国际免疫学杂志,2009,32(01)：47-51
[26]冯洁,臧国庆,余永胜.转录因子AP-1在肝病中的作用.肝脏,2007,12(5)：418-419
[27]Hang M H, Chou C M, Hsieh Y C, et al. Identification of 5'-upstream region of pufferfish ribosomal protein 129 gene a strongconstitutive pmmoter to drive GFP expression in zebrafish. Biochem Biophys Res Commun,2004,314:249-258
[28]McCarroll S A, Li H and Bargmann C I. Identification of Transcriptional Regulatory Elements in Chemosensory Receptor Genes by Probabilistic Segmentation. Current Biology, 2005,15:347-352
[29]Cooper S J and Nathan D. Comprehensive analysis of transcriptional promoter structure and function in 1% of the human genome. Genome Res,2006,16:1-10
[30]Peterson M J and Morris J F. Human myeloid zinc finger gene MZF produces multiple transcript and encodes a SCAN box protein. Gene,2000,254(1-2):105-118
[1]张春燕,邹平.表观遗传学及其研究进展.四川生理科学杂志,2006,28(2)：72-74
[2]Yu Y, Zhang H M, Tian F, et al. Quantitative Evaluation of DNA Methylation Patterns for ALVE and TVB Genes in a Neoplastic Disease Susceptible and Resistant Chicken Model PLoS ONE,2008,3(3):1-10
[3]Luo J, Yu Y, Zhang H M, et al. Down-regulation of Promoter Methylation Level of CD4 gene after MDV Infection in MD-susception Chicken line. BioMed Central (BMC) Genetics,2010, (5):25-31
[4]刘振山,李齐发,张庆波,等.犏牛及其亲本JGF2基因mRNA表达水平、DNA甲基化状态差异分析.自然科学进展,2009,19(4)：380-385
[5]Li Q H, Li N, Hu X X, et al. Genome-Wide Mapping of DNA Methylation in Chicken. PLoS ONE,2011,6(5):1-7
[6]Yang C, Zhang M J, Niu W P, et al. Analysis of DNA Methylation in Various Swine Tissues. PLoS ONE,2011,6(1):1-9
[7]田艳苓.鸡微卫星标记、DNA甲基化差异和FSHβ变异及其与体重和产蛋性状的关系.硕十学位论文,山东农业大学,2011
[8]蒋曹德,邓昌彦,熊远著.猪个体DNA甲基化百分差异与胴体性状的关系.农业生物技术学报,2005,13(2)：179-185
[9]谭小方,黄天华.HBV基因经生殖细胞垂直传播与DNA甲基化研究发展.癌变畸变突变,2008,20(3)：247-248
[10]Pestano G A, Zhou Y L, Trimble L A, et al. Inactivation of Misselected CD8 T Cells by CD8 Gene Methylation and Cell Death. Science,1999,28(4):1187-1191
[11]Hamerman J A, Page S T, Pullen A M. Distinct Methylation States of the CD8 Beta Gene in Peripheral T Cells and Intraeapithelial Lymphocytes. The Journal of Immunology,1997, 159(3):1240-1246
[12]Chen C, Chen H, Hsiau T, et al. Technical advance:methylation target array for rapid analysis of CPG island hypermethylation in multiple issue genomes. Am Pathol,2003,163(1): 37-45
[13]Shi H, Yan P S, Chen C, et al. ExPressed CpG island sequence tag microarray for screening of DNA hypermethylaion and gene silencing in cancer cells. Cancer Res,2002,62: 3214-3220
[14]Lander E S, Linton L M, Birren B, et al. Initial sequencing and analysis of the human genome. Nature,2001,409:860-921
[15]Takai, D. and Peter Jones. Comprehensive analysis of CpG islands in human chromosomes 21 and 22. PNAS,2002,99 (6):3740-3745
[16]Kawasaki T, Nosho K, Ohnishi M, et al. IGFBP3 Promoter Methylation in Colorectal Cancer: Relationship with Microsatellite Instability, CpG Island Methylator Phenotype, and p53, Neoplasia.2007,9(12):1091-1098
[17]Lai J C, Cheng Y W, Goan Y G, et al. Promoter methylation of O6-methy]guanine-DNA-methyltransferase in lung cancer is regulated by p53, DNA Repair, 2008,7(8):1352-1363
[18]Torng P L, Lin C W, Chan M W Y, et al. Promoter methylation of IGFBP-3 and p53 expression in ovarian endometrioid carcinoma, Molecular Cancer 2009,:120 doi:10.1186/1476-4598-8-120
[19]董瑞,赵瑞,郑珊,等.胆道闭锁患儿外周血T细胞ITGAL基因启动子区甲基化状态及其mRNA表达,中国循证儿科杂志,2011,6(3)：220-224
[20]Jeong Y S, Yeo S, Park J S, et al. DNA methylation state is preserved in the sperm-derived pronucleus of the pig zygote. Int. J. Dev. Biol.2007,51:707-714
[21]Yu Y, Zhang H M, Byerly M S, et al. Alternative splicing variants and DNA methylation status of BDNF in inbred chicken lines. BRAIN RESEARCH,2009,1-10
[22]凌飞,李加琪,王翀,等.猪脂联素基因启动子区甲基化与其mRNA表达分析,遗 传,2009,31(10)：1013-1019
[23]刘振山,李齐发,张庆波,等,犏牛及其亲本IGF2基因mRNA表达水平、DNA甲基化状态差异分析,自然科学进展,2009,9(4)：380-385
[24]荣美洁,李兰,董文娟.崂山奶山羊乳腺中孕激素受体基因甲基化与基因表达关系的研究,青岛农业大学学报(自然科学版),2010,27(3)：186-190
[25]Fan X, Inda M M, Tunon T, etal. Improvement of the methylation specific PCR technical conditions for the detection of p16 promoter hypermethylation in small amounts of tumor DNA. Oncol Rep,2002,9(1):181-183
[26]Zilberman D. The human promoter methylome. Nat Genet,2007,39(4):442-443
[27]Schutte M, Hruban R H, Geradts J, et al. Abrogation of the Rb/pl6 tumor-suppressive pathway in virtually all pancreatic carcinomas. Cancer Res,1997,57(15):3126-3130
[28]Gonzalgo M L, Hayashida T, Bender C M, et al. The role of DNA methylation in expression of the p19/p16 locus in human bladder cancer cell lines. Cancer Res,1998,58(6):1245-1252
[29]Brandeis M, Frank D, Keshet I, et al. Spl elements protect a CpG island from de novo methylation. Nature,1994,371(6496):435-438
[30]Macleod D, Charlton J, Mullins J, et al. Spl sites in the mouse aprt gene promoter are required to prevent methylation of the CpG island. Genes Dev,1994,8(19):2282-2292
[31]Brenner C, Deplus R, Didelot C. Myc represses transcription through recruitment of DNA methyltransferase corepressor. EMBO J,2005,24(2):336-346
[32]Di Croce L, Raker VA, Corsaro M, et al. Methyltransferase recruitment and DNA hypermethylation of target promoters by an oncogenic transcription factor. Science,2002, 295(5557):1079-1082
[33]Wu L M, Zhang F, Zhou L, et al. Predictive value of CpG island methylator phenotype for tumor recurrence in hepatitis B virus associated hepatocellular carcinoma following liver transplantation. BMC Cancer,2010,10:399
[34]Ehrlich. M. DNA methylation in cancer:too much, but also too little. Oncogene,2002,21(35): 5400-5413
[35]孔令敏,CD147基因的转录调控机制及其表观遗传修饰,第四军医大学学位论文,2010
[36]EDEN A, GAUDET F, WAGHMARE A, et al. Chromosomal instability and tumors promoted by DNA hypomethylation. Science,2003,300(5618):455
[37]FLORL A R, STEINHOF C, MULLER M, et al. Coordinate hypermethylation at specific genes in prostate carcinoma precedes L1NE-1 hypomethylation. Br J Cancer,2004,91(5): 985-994
[38]FEINBERG A P, TYCKO B. The history of cancer epigenetics. Nat Rev Cancer,2004,4(2): 143-153
[39]徐青.鸡DNA甲基化组织特异性及亲本与子代甲基化差异性研究,北京：中国农业大学博十论文,2006