奶牛乳腺炎致病机制的表观遗传调控研究进展
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摘要
奶牛乳腺炎作为制约奶牛养殖业发展的主要疾病之一,其受到环境、理化因素以及不同病原菌等多种因素影响。表观遗传调控作为一种新的分子调控机制,在奶牛乳腺炎致病过程中起着十分重要的作用。本文拟从DNA甲基化、组蛋白修饰和非编码RNA等多方面综述其在奶牛乳腺炎发生、发展中的作用,并从多维度提出奶牛乳腺炎表观遗传调控机制未来研究策略,以期为奶牛乳腺炎致病机制研究以及有效防控提供参考。
As one of the main diseases that impede the development of dairy cattle farming industry, cow mastitis is deeply influenced by environmental, physicochemical factors and different pathogenic bacteria. Epigenetic regulation, being a new molecular regulation mechanism, plays a very important role in the pathogenesis of cow mastitis. Here, the roles of DNA methylation, histone modification and non-coding RNA in the occurrence and development of cow mastitis were reviewed, and the future research strategies of the epigenetic regulation mechanism of cow mastitis were proposed in multi-dimension, in order to provide references for the pathogenesis research and effective prevention and control of cow mastitis.
As one of the main diseases that impede the development of dairy cattle farming industry, cow mastitis is deeply influenced by environmental, physicochemical factors and different pathogenic bacteria. Epigenetic regulation, being a new molecular regulation mechanism, plays a very important role in the pathogenesis of cow mastitis. Here, the roles of DNA methylation, histone modification and non-coding RNA in the occurrence and development of cow mastitis were reviewed, and the future research strategies of the epigenetic regulation mechanism of cow mastitis were proposed in multi-dimension, in order to provide references for the pathogenesis research and effective prevention and control of cow mastitis.
引文
[1]Swinkels J M,Hilkens A,Zoche-Golob V,et al.Social influences on the duration of antibiotic treatment of clinical mastitis in dairy cows[J].J Dairy Sci,2015,98(4):2369-2380.
[2]Bird A.Perceptions of epigenetics[J].Nature,2007,447(7143):396-398.
[3]Tajima S,Suetake I,Takeshita K,et al.Domain structure of the dnmt1,dnmt3a,and dnmt3b DNA methyltransferases[J].Adv Exp Med Biol,2016,945:63-86.
[4]Liao J,Karnik R,Gu H,et al.Targeted disruption of DNMT1,DNMT3A and DNMT3B in human embryonic stem cells[J].Nat Genet,2015,47(5):469-478.
[5]Cai T T,Zhang J,Wang X,et al.Gene-gene and gene-sex epistatic interactions of DNMT1,DNMT3A and DNMT3B in autoimmune thyroid disease[J].Endocr J,2016,63(7):643-653.
[6]Li H,Li W,Liu S,et al.DNMT1,DNMT3A and DNMT3Bpolymorphisms associated with gastric cancer risk:A systematic review and meta-analysis[J].EBio Medicine,2016,13:125-131.
[7]Mao Y J,Zhu X R,Li R,et al.Methylation analysis of CXCR1in mammary gland tissue of cows with mastitis induced by Staphylococcus aureus[J].Genet Mol Res,2015,14(4):12606-12615.
[8]Vanselow J,Yang W,Herrmann J,et al.DNA-remethylation around a STAT5-binding enhancer in the alphaS1-casein promoter is associated with abrupt shutdown of alphaS1-casein synthesis during acute mastitis[J].J Mol Endocrinol,2006,37(3):463-477.
[9]Wang X S,Zhang Y,He Y H,et al.Aberrant promoter methylation of the CD4 gene in peripheral blood cells of mastitic dairy cows[J].Genet Mol Res,2013,12(4):6228-6239.
[10]Song M,He Y,Zhou H,et al.Combined analysis of DNA methylome and transcriptome reveal novel candidate genes with susceptibility to bovine Staphylococcus aureus subclinical mastitis[J].Sci Rep,2016,6:29390.
[11]Kornberg R D,Lorch Y.Twenty-five years of the nucleosome,fundamental particle of the eukaryote chromosome[J].Cell,1999,98(3):285-294.
[12]Fischle W,Wang Y,Allis C D.Histone and chromatin crosstalk[J].Curr OpinCell Biol,2003,15(2):172-183.
[13]Peterson C L,Laniel M A.Histones and histone modifications[J].Curr Biol,2004,14(14):546-551.
[14]He Y,Song M,Zhang Y,et al.Whole-genome regulation analysis of histone H3 lysin 27 trimethylation in subclinical mastitis cows infected by Staphylococcus aureus[J].BMCGenomics,2016,17:565.
[15]Huang S,Chi Y,Qin Y,et al.CAPG enhances breast cancer metastasis by competing with PRMT5 to modulate STC-1transcription[J].Theranostics,2018,8(9):2549-2564.
[16]Modak R,Das Mitra S,Krishnamoorthy P,et al.Histone H3K14and H4K8 hyperacetylation is associated with Escherichia coliinduced mastitis in mice[J].Epigenetics,2012,7(5):492-501.
[17]Ochoa-Zarzosa A,Villarreal-Fernandez E,Cano-Camacho H,et al.Sodium butyrate inhibits Staphylococcus aureus internalization in bovine mammary epithelial cells and induces the expression of antimicrobial peptide genes[J].Microb Pathog,2009,47(1):1-7.
[18]Kutanzi K,Kovalchuk O.Exposure to estrogen and ionizing radiation causes epigenetic dysregulation,activation of mitogenactivated protein kinase pathways,and genome instability in the mammary gland of ACI rats[J].Cancer Biol Ther,2013,14(7):564-573.
[19]Wang B,Li D,Kovalchuk O.p53 Ser15 phosphorylation and histone modifications contribute to IR-induced miR-34a transcription in mammary epithelial cells[J].Cell Cycle,2013,12(13):2073-2083.
[20]Lan X,Atanassov B S,Li W,et al.USP44 Is an integral component of N-CoR that contributes to gene repression by deubiquitinating histone H2B[J].Cell Rep,2016,17(9):2382-2393.
[21]Bhatnagar S,Gazin C,Chamberlain L,et al.TRIM37 is a new histone H2A ubiquitin ligase and breast cancer oncoprotein[J].Nature,2014,516(7529):116-120.
[22]Strahl B D,Allis C D.The language of covalent histone modifications[J].Nature,2000,403(6765):41-45.
[23]Gondaira S,Higuchi H,Iwano H,et al.Innate immune response of bovine mammary epithelial cells to Mycoplasma bovis[J].JVet Sci,2018,19(1):79-87.
[24]Prenzel T,Begus-Nahrmann Y,Kramer F,et al.Estrogen-dependent gene transcription in human breast cancer cells relies upon proteasome-dependent monoubiquitination of histone H2B[J].Cancer Res,2011,71(17):5739-5753.
[25]Spolverini A,Fuchs G,Bublik D R,et al.let-7b and let-7c microRNAs promote histone H2B ubiquitylation and inhibit cell migration by targeting multiple components of the H2Bdeubiquitylation machinery[J].Oncogene,2017,36(42):5819-5828.
[26]Sun J,Aswath K,Schroeder S G,et al.MicroRNA exp-ression profiles of bovine milk exosomes in response to Staphylococcus aureus infection[J].BMC Genomics,2015,16:806.
[27]Naeem A,Zhong K,Moisa S J,et al.Bioinformatics analysis of microRNA and putative target genes in bovine mammary tissue infected with Streptococcus uberis[J].J Dairy Sci,2012,95(11):6397-6408.
[28]Jin W,Ibeagha-Awemu E M,Liang G,et al.Transcriptome micro RNA profiling of bovine mammary epithelial cells challenged with Escherichia coli or Staphylococcus aureus bacteria reveals pathogen directed microRNA expression profiles[J].BMCGenomics,2014,15:181.
[29]Kang L,Huo Y,Wang R F,et al.In vivo imaging of breast tumors by a(99m)Tc radiolabeled probe targeting microRNA-155 in mice models[J].Beijing Da Xue Xue Bao.Yi Xue Ban,2018,50(2):326-330.
[30]LeMay-Nedjelski L,Mason-Ennis J K,Taibi A,et al.Omega-3polyunsaturated fatty acids time-dependently reduce cell viability and oncogenic microRNA-21 expression in estrogen receptor-positive breast cancer cells(MCF-7)[J].Int J Mol Sci,2018,19(1):244.
[31]Wang X P,Luoreng Z M,Zan L S,et al.Expression patterns of miR-146a and miR-146b in mastitis infected dairy cattle[J].Mol Cell Probes,2016,30(5):342-344.
[32]Yang W,Li X,Qi S,et al.lncRNA H19 is involved in TGF-beta1-induced epithelial to mesenchymal transition in bovine epithelial cells through PI3K/AKT Signaling Pathway[J].Peer J,2017,5:1-15.
[33]Silva J M,Boczek N J,Berres M W,et al.LSINCT5 is over ex-pressed in breast and ovarian cancer and affects cellular proliferation[J].RNA Biology,2011,8(3):496-505.
[34]Huang J,Zhou N,Watabe K,et al.Long non-coding RNAUCA1 promotes breast tumor growth by suppression of p27(Kip1)[J].Cell Death Dis,2014,5:1-10.
[35]Lanz R B,Chua S S,Barron N,et al.Steroid receptor RNAactivator stimulates proliferation as well as apoptosis in vivo[J].Mol Cell Biol,2003,23(20):7163-7176.
[36]Ginger M R,Gonzalez-Rimbau M F,Gay J P,et al.Persistent c h a n g e s i n g e n e e x p r e s s i o n i n d u c e d b y e s t r o g e n a n d progesterone in the rat mammary gland[J].Mol Endocrinol,2001,15(11):1993-2009.
[37]Wang H,Xiao Y,Wu L,et al.Comprehensive circular RNAprofiling reveals the regulatory role of the circRNA-000911/miR-449a pathway in breast carcinogenesis[J].Int J Oncol,2018,52(3):743-754.
[38]Zhou J,Zhang W W,Peng F,et al.Downregulation of hsa_circ_0011946 suppresses the migration and invasion of the breast cancer cell line MCF-7 by targeting RFC3[J].Cancer Manag Res,2018,10:535-544.
[39]Yan N,Xu H,Zhang J,et al.Circular RNA profile indicates circular RNA VRK1 is negatively related with breast cancer stem cells[J].Oncotarget,2017,8(56):95704-95718.
[40]Lee J T.Epigenetic regulation by long noncoding RNAs[J].Science,2012,338(6113):1435-1439.
[41]Bonasio R,Shiekhattar R.Regulation of transcription by long noncoding RNAs[J].Annu Rev Genet,2014,48:433-455.
[42]Yoon J H,Abdelmohsen K,Gorospe M.Posttranscriptional gene regulation by long noncoding RNA[J].J Mol Biol,2013,425(19):3723-3730.
[43]Shore A N,Rosen J M.Regulation of mammary epithelial cell homeostasis by lncRNAs[J].Int J Biochem Cell Biol,2014,54:318-330.
[44]Standaert L,Adriaens C,Radaelli E,et al.The long noncoding RNA Neat1 is required for mammary gland development and lactation[J].RNA,2014,20(12):1844-1849.
[45]Lo P K,Wolfson B,Zhou X,et al.Noncoding RNAs in breast cancer[J].Briefings Funct Genomics,2016,15(3):200-221.
[46]Tong C,Chen Q,Zhao L,et al.Identification and characterization of long intergenic noncoding RNAs in bovine mammary glands[J].BMC Genomics,2017,18(1):468.
[47]Preusser C,Hung L H,Schneider T,et al.Selective release of circRNAs in platelet-derived extracellular vesicles[J].JExtracell Vesicles,2018,7(1):1424473.
[48]Zhang C,Wu H,Wang Y,et al.Expression patterns of circular RNAs from primary kinase transcripts in the mammary glands of lactating rats[J].J Breast Cancer,2015,18(3):235-241.
[49]Liao J Y,Wu J,Wang Y J,et al.Deep sequencing reveals a global reprogramming of lncRNA transcriptome during EMT[J].Biochim Biophys Acta Mol Cell Res,2017,1864(10):1703-1713.
[50]Zhang C,Wu H,Wang Y,et al.Circular RNA of cattle casein genes are highly expressed in bovine mammary gland[J].JDairy Sci,2016,99(6):4750-4760.
[51]Su J,Qi Y,Liu S,et al.Revealing epigenetic patterns in gene regulation through integrative analysis of epigenetic interaction network[J].Mol Biol Rep,2012,39(2):1701-1712.
[52]Rothbart S B,Krajewski K,Nady N,et al.Association of UHRF1 with methylated H3K9 directs the maintenance of DNA methylation[J].Nat Struct Mol Biol,2012,19(11):1155-1160.
[53]Zhang X,Zhao X,Fiskus W,et al.Coordinated silencing of MYC-mediated miR-29 by HDAC3 and EZH2 as a therapeutic target of histone modification in aggressive B-Cell lymphomas[J].Cancer Cell,2012,22(4):506-523.
[54]Li M A,Amaral P P,Cheung P,et al.A lncRNA fine tunes the dynamics of a cell state transition involving Lin28,let-7 and de novo DNA methylation[J].eLife,2017,6:1-24.
[55]Zhou J,Yang L,Zhong T,et al.H19 lncRNA alters DNAmethylation genome wide by regulating S-adenosylhomocysteine hydrolase[J].Nat Commun,2015,6:10221.
[56]Oertel B G,Doehring A,Roskam B,et al.Genetic-epigenetic interaction modulates mu-opioid receptor regulation[J].Hum Mol Genet,2012,21(21):4751-4760.
[57]Kalin J H,Wu M,Gomez A V,et al.Targeting the CoRESTcomplex with dual histone deacetylase and demethylase inhibitors[J].Nat Com,2018,9(1):53.
[2]Bird A.Perceptions of epigenetics[J].Nature,2007,447(7143):396-398.
[3]Tajima S,Suetake I,Takeshita K,et al.Domain structure of the dnmt1,dnmt3a,and dnmt3b DNA methyltransferases[J].Adv Exp Med Biol,2016,945:63-86.
[4]Liao J,Karnik R,Gu H,et al.Targeted disruption of DNMT1,DNMT3A and DNMT3B in human embryonic stem cells[J].Nat Genet,2015,47(5):469-478.
[5]Cai T T,Zhang J,Wang X,et al.Gene-gene and gene-sex epistatic interactions of DNMT1,DNMT3A and DNMT3B in autoimmune thyroid disease[J].Endocr J,2016,63(7):643-653.
[6]Li H,Li W,Liu S,et al.DNMT1,DNMT3A and DNMT3Bpolymorphisms associated with gastric cancer risk:A systematic review and meta-analysis[J].EBio Medicine,2016,13:125-131.
[7]Mao Y J,Zhu X R,Li R,et al.Methylation analysis of CXCR1in mammary gland tissue of cows with mastitis induced by Staphylococcus aureus[J].Genet Mol Res,2015,14(4):12606-12615.
[8]Vanselow J,Yang W,Herrmann J,et al.DNA-remethylation around a STAT5-binding enhancer in the alphaS1-casein promoter is associated with abrupt shutdown of alphaS1-casein synthesis during acute mastitis[J].J Mol Endocrinol,2006,37(3):463-477.
[9]Wang X S,Zhang Y,He Y H,et al.Aberrant promoter methylation of the CD4 gene in peripheral blood cells of mastitic dairy cows[J].Genet Mol Res,2013,12(4):6228-6239.
[10]Song M,He Y,Zhou H,et al.Combined analysis of DNA methylome and transcriptome reveal novel candidate genes with susceptibility to bovine Staphylococcus aureus subclinical mastitis[J].Sci Rep,2016,6:29390.
[11]Kornberg R D,Lorch Y.Twenty-five years of the nucleosome,fundamental particle of the eukaryote chromosome[J].Cell,1999,98(3):285-294.
[12]Fischle W,Wang Y,Allis C D.Histone and chromatin crosstalk[J].Curr OpinCell Biol,2003,15(2):172-183.
[13]Peterson C L,Laniel M A.Histones and histone modifications[J].Curr Biol,2004,14(14):546-551.
[14]He Y,Song M,Zhang Y,et al.Whole-genome regulation analysis of histone H3 lysin 27 trimethylation in subclinical mastitis cows infected by Staphylococcus aureus[J].BMCGenomics,2016,17:565.
[15]Huang S,Chi Y,Qin Y,et al.CAPG enhances breast cancer metastasis by competing with PRMT5 to modulate STC-1transcription[J].Theranostics,2018,8(9):2549-2564.
[16]Modak R,Das Mitra S,Krishnamoorthy P,et al.Histone H3K14and H4K8 hyperacetylation is associated with Escherichia coliinduced mastitis in mice[J].Epigenetics,2012,7(5):492-501.
[17]Ochoa-Zarzosa A,Villarreal-Fernandez E,Cano-Camacho H,et al.Sodium butyrate inhibits Staphylococcus aureus internalization in bovine mammary epithelial cells and induces the expression of antimicrobial peptide genes[J].Microb Pathog,2009,47(1):1-7.
[18]Kutanzi K,Kovalchuk O.Exposure to estrogen and ionizing radiation causes epigenetic dysregulation,activation of mitogenactivated protein kinase pathways,and genome instability in the mammary gland of ACI rats[J].Cancer Biol Ther,2013,14(7):564-573.
[19]Wang B,Li D,Kovalchuk O.p53 Ser15 phosphorylation and histone modifications contribute to IR-induced miR-34a transcription in mammary epithelial cells[J].Cell Cycle,2013,12(13):2073-2083.
[20]Lan X,Atanassov B S,Li W,et al.USP44 Is an integral component of N-CoR that contributes to gene repression by deubiquitinating histone H2B[J].Cell Rep,2016,17(9):2382-2393.
[21]Bhatnagar S,Gazin C,Chamberlain L,et al.TRIM37 is a new histone H2A ubiquitin ligase and breast cancer oncoprotein[J].Nature,2014,516(7529):116-120.
[22]Strahl B D,Allis C D.The language of covalent histone modifications[J].Nature,2000,403(6765):41-45.
[23]Gondaira S,Higuchi H,Iwano H,et al.Innate immune response of bovine mammary epithelial cells to Mycoplasma bovis[J].JVet Sci,2018,19(1):79-87.
[24]Prenzel T,Begus-Nahrmann Y,Kramer F,et al.Estrogen-dependent gene transcription in human breast cancer cells relies upon proteasome-dependent monoubiquitination of histone H2B[J].Cancer Res,2011,71(17):5739-5753.
[25]Spolverini A,Fuchs G,Bublik D R,et al.let-7b and let-7c microRNAs promote histone H2B ubiquitylation and inhibit cell migration by targeting multiple components of the H2Bdeubiquitylation machinery[J].Oncogene,2017,36(42):5819-5828.
[26]Sun J,Aswath K,Schroeder S G,et al.MicroRNA exp-ression profiles of bovine milk exosomes in response to Staphylococcus aureus infection[J].BMC Genomics,2015,16:806.
[27]Naeem A,Zhong K,Moisa S J,et al.Bioinformatics analysis of microRNA and putative target genes in bovine mammary tissue infected with Streptococcus uberis[J].J Dairy Sci,2012,95(11):6397-6408.
[28]Jin W,Ibeagha-Awemu E M,Liang G,et al.Transcriptome micro RNA profiling of bovine mammary epithelial cells challenged with Escherichia coli or Staphylococcus aureus bacteria reveals pathogen directed microRNA expression profiles[J].BMCGenomics,2014,15:181.
[29]Kang L,Huo Y,Wang R F,et al.In vivo imaging of breast tumors by a(99m)Tc radiolabeled probe targeting microRNA-155 in mice models[J].Beijing Da Xue Xue Bao.Yi Xue Ban,2018,50(2):326-330.
[30]LeMay-Nedjelski L,Mason-Ennis J K,Taibi A,et al.Omega-3polyunsaturated fatty acids time-dependently reduce cell viability and oncogenic microRNA-21 expression in estrogen receptor-positive breast cancer cells(MCF-7)[J].Int J Mol Sci,2018,19(1):244.
[31]Wang X P,Luoreng Z M,Zan L S,et al.Expression patterns of miR-146a and miR-146b in mastitis infected dairy cattle[J].Mol Cell Probes,2016,30(5):342-344.
[32]Yang W,Li X,Qi S,et al.lncRNA H19 is involved in TGF-beta1-induced epithelial to mesenchymal transition in bovine epithelial cells through PI3K/AKT Signaling Pathway[J].Peer J,2017,5:1-15.
[33]Silva J M,Boczek N J,Berres M W,et al.LSINCT5 is over ex-pressed in breast and ovarian cancer and affects cellular proliferation[J].RNA Biology,2011,8(3):496-505.
[34]Huang J,Zhou N,Watabe K,et al.Long non-coding RNAUCA1 promotes breast tumor growth by suppression of p27(Kip1)[J].Cell Death Dis,2014,5:1-10.
[35]Lanz R B,Chua S S,Barron N,et al.Steroid receptor RNAactivator stimulates proliferation as well as apoptosis in vivo[J].Mol Cell Biol,2003,23(20):7163-7176.
[36]Ginger M R,Gonzalez-Rimbau M F,Gay J P,et al.Persistent c h a n g e s i n g e n e e x p r e s s i o n i n d u c e d b y e s t r o g e n a n d progesterone in the rat mammary gland[J].Mol Endocrinol,2001,15(11):1993-2009.
[37]Wang H,Xiao Y,Wu L,et al.Comprehensive circular RNAprofiling reveals the regulatory role of the circRNA-000911/miR-449a pathway in breast carcinogenesis[J].Int J Oncol,2018,52(3):743-754.
[38]Zhou J,Zhang W W,Peng F,et al.Downregulation of hsa_circ_0011946 suppresses the migration and invasion of the breast cancer cell line MCF-7 by targeting RFC3[J].Cancer Manag Res,2018,10:535-544.
[39]Yan N,Xu H,Zhang J,et al.Circular RNA profile indicates circular RNA VRK1 is negatively related with breast cancer stem cells[J].Oncotarget,2017,8(56):95704-95718.
[40]Lee J T.Epigenetic regulation by long noncoding RNAs[J].Science,2012,338(6113):1435-1439.
[41]Bonasio R,Shiekhattar R.Regulation of transcription by long noncoding RNAs[J].Annu Rev Genet,2014,48:433-455.
[42]Yoon J H,Abdelmohsen K,Gorospe M.Posttranscriptional gene regulation by long noncoding RNA[J].J Mol Biol,2013,425(19):3723-3730.
[43]Shore A N,Rosen J M.Regulation of mammary epithelial cell homeostasis by lncRNAs[J].Int J Biochem Cell Biol,2014,54:318-330.
[44]Standaert L,Adriaens C,Radaelli E,et al.The long noncoding RNA Neat1 is required for mammary gland development and lactation[J].RNA,2014,20(12):1844-1849.
[45]Lo P K,Wolfson B,Zhou X,et al.Noncoding RNAs in breast cancer[J].Briefings Funct Genomics,2016,15(3):200-221.
[46]Tong C,Chen Q,Zhao L,et al.Identification and characterization of long intergenic noncoding RNAs in bovine mammary glands[J].BMC Genomics,2017,18(1):468.
[47]Preusser C,Hung L H,Schneider T,et al.Selective release of circRNAs in platelet-derived extracellular vesicles[J].JExtracell Vesicles,2018,7(1):1424473.
[48]Zhang C,Wu H,Wang Y,et al.Expression patterns of circular RNAs from primary kinase transcripts in the mammary glands of lactating rats[J].J Breast Cancer,2015,18(3):235-241.
[49]Liao J Y,Wu J,Wang Y J,et al.Deep sequencing reveals a global reprogramming of lncRNA transcriptome during EMT[J].Biochim Biophys Acta Mol Cell Res,2017,1864(10):1703-1713.
[50]Zhang C,Wu H,Wang Y,et al.Circular RNA of cattle casein genes are highly expressed in bovine mammary gland[J].JDairy Sci,2016,99(6):4750-4760.
[51]Su J,Qi Y,Liu S,et al.Revealing epigenetic patterns in gene regulation through integrative analysis of epigenetic interaction network[J].Mol Biol Rep,2012,39(2):1701-1712.
[52]Rothbart S B,Krajewski K,Nady N,et al.Association of UHRF1 with methylated H3K9 directs the maintenance of DNA methylation[J].Nat Struct Mol Biol,2012,19(11):1155-1160.
[53]Zhang X,Zhao X,Fiskus W,et al.Coordinated silencing of MYC-mediated miR-29 by HDAC3 and EZH2 as a therapeutic target of histone modification in aggressive B-Cell lymphomas[J].Cancer Cell,2012,22(4):506-523.
[54]Li M A,Amaral P P,Cheung P,et al.A lncRNA fine tunes the dynamics of a cell state transition involving Lin28,let-7 and de novo DNA methylation[J].eLife,2017,6:1-24.
[55]Zhou J,Yang L,Zhong T,et al.H19 lncRNA alters DNAmethylation genome wide by regulating S-adenosylhomocysteine hydrolase[J].Nat Commun,2015,6:10221.
[56]Oertel B G,Doehring A,Roskam B,et al.Genetic-epigenetic interaction modulates mu-opioid receptor regulation[J].Hum Mol Genet,2012,21(21):4751-4760.
[57]Kalin J H,Wu M,Gomez A V,et al.Targeting the CoRESTcomplex with dual histone deacetylase and demethylase inhibitors[J].Nat Com,2018,9(1):53.