DNA甲基化和组蛋白甲基化修饰的表观遗传调控作用研究进展

doi:10.13560/j.cnki.biotech.bull.1985.2021-1054

摘要/Abstract

摘要：

在真核生物中,作为表观遗传调控的常见机制,DNA甲基化和组蛋白甲基化主要影响染色质结构和基因的转录表达,特别是在哺乳动物细胞基因表达调控、维持基因组稳定性等方面起着重要的作用。本文综述了DNA甲基化修饰及其基因表达调控作用;组蛋白甲基化修饰的基因表达调控方式、功能及其研究进展;以及DNA甲基化和组蛋白甲基化在表观遗传调控方面的相互作用。

关键词: 基因表达, 表观遗传调控, DNA甲基化, 组蛋白甲基化

Abstract:

In eukaryotes,as a common mechanism of epigenetic regulation,DNA and histone methylations mainly affect chromatin structure and gene transcription expression,especially in gene expression regulation of mammalian cells and maintaining genome stability. This paper reviews DNA methylation modification and its role in gene expression regulation,gene expression regulation mode,function and research progress of histone methylation modification,as well as the interaction between DNA and histone methylations in epigenetic regulation.

Key words: gene expression, epigenetic regulation, DNA methylation, histone methylation

张淼, 杨露露, 贾岩龙, 王天云. DNA甲基化和组蛋白甲基化修饰的表观遗传调控作用研究进展[J]. 生物技术通报, 2022, 38(7): 23-30.

ZHANG Miao, YANG Lu-lu, JIA Yan-long, WANG Tian-yun. Research Progress in the Roles of DNA and Histone Methylations in Epigenetic Regulation[J]. Biotechnology Bulletin, 2022, 38(7): 23-30.

图/表 2

参考文献 63

[1]	Borck PC, Guo LW, Plutzky J. BET epigenetic reader proteins in cardiovascular transcriptional programs[J]. Circ Res, 2020, 126(9):1190-1208. doi: 10.1161/CIRCRESAHA.120.315929 URL
[2]	陈香嵩. 组蛋白甲基化与DNA甲基化的相互作用及其表观遗传机制的研究[D]. 武汉: 华中农业大学, 2012.
	Chen XS. Study on interaction and epigenetic inheritance of histone and DNA methylaton[D]. Wuhan: Huazhong Agricultural University, 2012.
[3]	Morgan AE, Davies TJ, Mc Auley MT. The role of DNA methylation in ageing and cancer[J]. Proc Nutr Soc, 2018, 77(4):412-422. doi: 10.1017/S0029665118000150 pmid: 29708096
[4]	Deaton AM, Bird A. CpG Islands and the regulation of transcription[J]. Genes Dev, 2011, 25(10):1010-1022. doi: 10.1101/gad.2037511 URL
[5]	Chen TP. Mechanistic and functional links between histone methylation and DNA methylation[J]. Prog Mol Biol Transl Sci, 2011, 101:335-348.
[6]	Luo CY, Hajkova P, Ecker JR. Dynamic DNA methylation:In the right place at the right time[J]. Science, 2018, 361(6409):1336-1340. doi: 10.1126/science.aat6806 URL
[7]	马雪山. 小鼠合子中DNA甲基化和H3K9me2修饰的变化及调控机制研究[D]. 南京: 南京农业大学, 2011.
	Ma XS. The dynamic and regulation mechanism of DNA methylation and H3K9me2 in mouse zygotes[D]. Nanjing: Nanjing Agricultural University, 2011.
[8]	Li HW, Rauch T, Chen ZX, et al. The histone methyltransferase SETDB1 and the DNA methyltransferase DNMT3A interact directly and localize to promoters silenced in cancer cells[J]. J Biol Chem, 2006, 281(28):19489-19500. doi: 10.1074/jbc.M513249200 URL
[9]	Desjobert C, El Maï M, Gérard-Hirne T,et al. Combined analysis of DNA methylation and cell cycle in cancer cells[J]. Epigenetics, 2015, 10(1):82-91. doi: 10.1080/15592294.2014.995542 pmid: 25531272
[10]	Greenberg MVC, Bourc'his D. The diverse roles of DNA methylation in mammalian development and disease[J]. Nat Rev Mol Cell Biol, 2019, 20(10):590-607. doi: 10.1038/s41580-019-0159-6 URL
[11]	Miller CA, Sweatt JD. Covalent modification of DNA regulates memory formation[J]. Neuron, 2007, 53(6):857-869. doi: 10.1016/j.neuron.2007.02.022 URL
[12]	Rose NR, Klose RJ. Understanding the relationship between DNA methylation and histone lysine methylation[J]. Biochim Biophys Acta, 2014, 1839(12):1362-1372.
[13]	钟焱, 徐慧, 彭凤兰. DNA甲基化在基因表达调控中的意义及研究进展[J]. 中国医药导报, 2019, 16(14):33-36.
	Zhong Y, Xu H, Peng FL. Significance and research progress of DNA methylation in gene expression regulation[J]. China Med Her, 2019, 16(14):33-36.
[14]	Suzuki T, Yamashita S, Ushijima T, et al. Genome-wide analysis of DNA methylation changes induced by gestational arsenic exposure in liver tumors[J]. Cancer Sci, 2013, 104(12):1575-1585. doi: 10.1111/cas.12298 URL
[15]	Aran D, Sabato S, Hellman A. DNA methylation of distal regulatory sites characterizes dysregulation of cancer genes[J]. Genome Biol, 2013, 14(3):R21. doi: 10.1186/gb-2013-14-3-r21 URL
[16]	Arney KL, Bae E, Olsen C, et al. The human and mouse H19 imprinting control regions harbor an evolutionarily conserved silencer element that functions on transgenes in Drosophila[J]. Dev Genes Evol, 2006, 216(12):811-819. doi: 10.1007/s00427-006-0102-7 URL
[17]	Soda K. Polyamine metabolism and gene methylation in conjunction with one-carbon metabolism[J]. Int J Mol Sci, 2018, 19(10):3106. doi: 10.3390/ijms19103106 URL
[18]	Du JM, Johnson LM, Jacobsen SE, et al. DNA methylation pathways and their crosstalk with histone methylation[J]. Nat Rev Mol Cell Biol, 2015, 16(9):519-532.
[19]	霍中军, 陈芳, 罗自勉. DNA甲基转移酶3A基因与肿瘤发生的分子调控机制研究进展[J]. 现代肿瘤医学, 2018, 26(20):3325-3329.
	Huo ZJ, Chen F, Luo ZM. Molecular mechanism of DNA methyltransferase 3A and tumorigenesis[J]. J Mod Oncol, 2018, 26(20):3325-3329.
[20]	Wang YZ, Xie YT, Li XF, et al. MiR-876-5p Acts as an inhibitor in hepatocellular carcinoma progression by targeting DNMT3A[J]. Pathol Res Pract, 2018, 214(7):1024-1030. doi: 10.1016/j.prp.2018.04.012 URL
[21]	Jia YL, Guo X, Lu JT, et al. CRISPR/Cas9-mediated gene knockout for DNA methyltransferase Dnmt3a in CHO cells displays enhanced transgenic expression and long-term stability[J]. J Cell Mol Med, 2018, 22(9):4106-4116. doi: 10.1111/jcmm.13687 URL
[22]	王佳贤. 利用crispr/cas9技术在CHO细胞和HEK293T细胞中敲除DNMT3a基因及在CHO细胞中定点整合CTLA4Ig基因[D]. 上海: 上海交通大学, 2016.
	Wang JX. Knockout of DNMT3a gene in both CHO and HEK293T cells as well as targeted integration of CTLA4Ig gene in CHO cells via crispr/Cas9 technology[D]. Shanghai: Shanghai Jiaotong University, 2016.
[23]	Bhattacharyya S, Mattiroli F, Luger K. Archaeal DNA on the histone merry-go-round[J]. FEBS J, 2018, 285(17):3168-3174. doi: 10.1111/febs.14495 pmid: 29729078
[24]	Fu WK, Gao L, Huang CF, et al. Mechanisms and importance of histone modification enzymes in targeted therapy for hepatobiliary cancers[J]. Discov Med, 2019, 28(151):17-28.
[25]	Zhang YJ, Sun ZX, Jia JQ, et al. Overview of histone modification[J]. Adv Exp Med Biol, 2021, 1283:1-16.
[26]	Nwasike C, Ewert S, Jovanovic S, et al. SET domain-mediated lysine methylation in lower organisms regulates growth and transcription in hosts[J]. Ann N Y Acad Sci, 2016, 1376(1):18-28. doi: 10.1111/nyas.13017 URL
[27]	Hublitz P, Albert M, Peters AHFM. Mechanisms of transcriptional repression by histone lysine methylation[J]. Int J Dev Biol, 2009, 53(2/3):335-354. doi: 10.1387/ijdb.082717ph URL
[28]	Black JC, Van Rechem C, Whetstine JR. Histone lysine methylation dynamics:establishment, regulation, and biological impact[J]. Mol Cell, 2012, 48(4):491-507. doi: 10.1016/j.molcel.2012.11.006 URL
[29]	Hanna CW, Taudt A, Huang J, et al. MLL2 conveys transcription-independent H3K4 trimethylation in oocytes[J]. Nat Struct Mol Biol, 2018, 25(1):73-82. doi: 10.1038/s41594-017-0014-4 URL
[30]	Sasidharan Nair V, El Salhat H, Taha RZ, et al. DNA methylation and repressive H3K9 and H3K27 trimethylation in the promoter regions of PD-1, CTLA-4, TIM-3, LAG-3, TIGIT, and PD-L1 genes in human primary breast cancer[J]. Clin Epigenetics, 2018, 10:78. doi: 10.1186/s13148-018-0512-1 pmid: 29983831
[31]	Weinberg DN, Papillon-Cavanagh S, Chen H, et al. The histone mark H3K36me2 recruits DNMT3A and shapes the intergenic DNA methylation landscape[J]. Nature, 2019, 573(7773):281-286. doi: 10.1038/s41586-019-1534-3 URL
[32]	Yang HN, Kwon CS, Choi Y, et al. Both H4K20 mono-methylation and H3K56 acetylation mark transcription-dependent histone turnover in fission yeast[J]. Biochem Biophys Res Commun, 2016, 476(4):515-521. doi: 10.1016/j.bbrc.2016.05.155 URL
[33]	Shailesh H, Zakaria ZZ, Baiocchi R, et al. Protein arginine methyltransferase 5(PRMT5)dysregulation in cancer[J]. Oncotarget, 2018, 9(94):36705-36718. doi: 10.18632/oncotarget.26404 URL
[34]	Izzo A, Schneider R. Chatting histone modifications in mammals[J]. Brief Funct Genomics, 2010, 9(5/6):429-443. doi: 10.1093/bfgp/elq024 URL
[35]	Beacon TH, Xu W, Davie JR. Genomic landscape of transcriptionally active histone arginine methylation marks, H3R2me2s and H4R3me2a, relative to nucleosome depleted regions[J]. Gene, 2020, 742:144593. doi: 10.1016/j.gene.2020.144593 URL
[36]	Qi H, Shi X, Yu M, et al. Sirtuin 7-mediated deacetylation of WD repeat domain 77(WDR77)suppresses cancer cell growth by reducing WDR77/PRMT5 transmethylase complex activity[J]. J Biol Chem, 2018, 293(46):17769-17779. doi: 10.1074/jbc.RA118.003629 URL
[37]	Majumder S, Alinari L, Roy S, et al. Methylation of histone H3 and H4 by PRMT5 regulates ribosomal RNA gene transcription[J]. J Cell Biochem, 2010, 109(3):553-563. doi: 10.1002/jcb.22432 pmid: 19998411
[38]	孙瑞, 樊红. 组蛋白赖氨酸甲基化修饰与胃癌发病机制相关性的研究进展[J]. 东南大学学报:医学版, 2019, 38(3):536-540.
	Sun R, Fan H. Research progress on the correlation between histone lysine methylation and the pathogenesis of gastric cancer[J]. J Southeast Univ:Med Sci Ed, 2019, 38(3):536-540.
[39]	Jih G, Iglesias N, Currie MA, et al. Unique roles for histone H3K9me states in RNAi and heritable silencing of transcription[J]. Nature, 2017, 547(7664):463-467. doi: 10.1038/nature23267 URL
[40]	Vavouri T, Lehner B. Human genes with CpG island promoters have a distinct transcription-associated chromatin organization[J]. Genome Biol, 2012, 13(11):R110. doi: 10.1186/gb-2012-13-11-r110 URL
[41]	Towbin BD, González-Aguilera C, Sack R, et al. Step-wise methylation of histone H3K9 positions heterochromatin at the nuclear periphery[J]. Cell, 2012, 150(5):934-947. doi: 10.1016/j.cell.2012.06.051 URL
[42]	Brower-Toland B, Riddle NC, Jiang H, et al. Multiple SET methyltransferases are required to maintain normal heterochromatin domains in the genome of Drosophila melanogaster[J]. Genetics, 2009, 181(4):1303-1319. doi: 10.1534/genetics.108.100271 pmid: 19189944
[43]	Hyun K, Jeon J, Park K, et al. Writing, erasing and reading histone lysine methylations[J]. Exp Mol Med, 2017, 49(4):e324.
[44]	Shuai WD, Wu JX, Chen S, et al. SUV39H2 promotes colorectal cancer proliferation and metastasis via tri-methylation of the SLIT1 promoter[J]. Cancer Lett, 2018, 422:56-69. doi: 10.1016/j.canlet.2018.02.023 URL
[45]	Muramatsu D, Singh PB, Kimura H, et al. Pericentric heterochromatin generated by HP₁ protein interaction-defective histone methyltransferase Suv39h1[J]. J Biol Chem, 2013, 288(35):25285-25296. doi: 10.1074/jbc.M113.470724 pmid: 23836914
[46]	van Wijnen AJ, Bagheri L, Badreldin AA, et al. Biological functions of chromobox(CBX)proteins in stem cell self-renewal, lineage-commitment, cancer and development[J]. Bone, 2021, 143:115659. doi: 10.1016/j.bone.2020.115659 URL
[47]	Maksimov DA, Koryakov DE. Binding of SU(VAR)₃-9 partially depends on SETDB1 in the chromosomes of Drosophila melanogaster[J]. Cells, 2019, 8(9):1030. doi: 10.3390/cells8091030 URL
[48]	Crawford NT, McIntyre AJ, McCormick A, et al. TBX2 interacts with heterochromatin protein 1 to recruit a novel repression complex to EGR1-targeted promoters to drive the proliferation of breast cancer cells[J]. Oncogene, 2019, 38(31):5971-5986. doi: 10.1038/s41388-019-0853-z pmid: 31253870
[49]	Hwang YJ, Han D, Kim KY, et al. ESET methylates UBF at K232/254 and regulates nucleolar heterochromatin plasticity and rDNA transcription[J]. Nucleic Acids Res, 2014, 42(3):1628-1643. doi: 10.1093/nar/gkt1041 pmid: 24234436
[50]	Casciello F, Al-Ejeh F, Kelly G, et al. G9a drives hypoxia-mediated gene repression for breast cancer cell survival and tumorigenesis[J]. PNAS, 2017, 114(27):7077-7082. doi: 10.1073/pnas.1618706114 URL
[51]	Ferry L, Fournier A, Tsusaka T, et al. Methylation of DNA ligase 1 by G9a/GLP recruits UHRF₁ to replicating DNA and regulates DNA methylation[J]. Mol Cell, 2017, 67(4):550-565. e5. doi: 10.1016/j.molcel.2017.07.012 URL
[52]	刘婉莹, 陈佳琪, 杨帆, 等. 组蛋白H3赖氨酸位点甲基化修饰对骨骼肌细胞分化的调控作用[J]. 医学信息, 2020, 33(7):24-28.
	Liu WY, Chen JQ, Yang F, et al. Regulation effect of methylation modification of histone H3 lysine on skeletal muscle cell differentiation[J]. Med Inf, 2020, 33(7):24-28.
[53]	Xie LL, Lin L, Huang SH, et al. Inhibition of Suv39H1 enhances transgenic IFNα-2b gene expression in Bcap-37 cells[J]. Anim Biotechnol, 2019, 30(4):358-365. doi: 10.1080/10495398.2018.1500373 URL
[54]	Blagitko-Dorfs N, Schlosser P, Greve G, et al. Combination treatment of acute myeloid leukemia cells with DNMT and HDAC inhibitors:predominant synergistic gene downregulation associated with gene body demethylation[J]. Leukemia, 2019, 33(4):945-956. doi: 10.1038/s41375-018-0293-8 pmid: 30470836
[55]	Sarraf SA, Stancheva I. Methyl-CpG binding protein MBD1 couples histone H3 methylation at lysine 9 by SETDB1 to DNA replication and chromatin assembly[J]. Mol Cell, 2004, 15(4):595-605. doi: 10.1016/j.molcel.2004.06.043 URL
[56]	Takada I, Mihara M, Suzawa M, et al. A histone lysine methyltransferase activated by non-canonical Wnt signalling suppresses PPAR-gamma transactivation[J]. Nat Cell Biol, 2007, 9(11):1273-1285. doi: 10.1038/ncb1647 URL
[57]	Dong CF, Wu YD, Yao J, et al. G9a interacts with Snail and is critical for Snail-mediated E-cadherin repression in human breast cancer[J]. J Clin Invest, 2012, 122(4):1469-1486. doi: 10.1172/JCI57349 URL
[58]	Chen MW, Hua KT, Kao HJ, et al. H3K9 histone methyltransferase G9a promotes lung cancer invasion and metastasis by silencing the cell adhesion molecule Ep-CAM[J]. Cancer Res, 2010, 70(20):7830-7840. doi: 10.1158/0008-5472.CAN-10-0833 URL
[59]	Hashimoto H, Vertino PM, Cheng X. Molecular coupling of DNA methylation and histone methylation[J]. Epigenomics, 2010, 2(5):657-669. pmid: 21339843
[60]	沈松菲. 急性白血病组蛋白甲基化和DNA甲基化的相互作用及对Wnt信号通路的调控研究[D]. 福州: 福建医科大学, 2011.
	Shen SF. Research on the interactions between histone and DNA methylation in acute leukemia and the regulation of wnt signal pathway[D]. Fuzhou: Fujian Medical University, 2011.
[61]	Minkovsky A, Sahakyan A, Rankin-Gee E, et al. The Mbd1-Atf7ip-Setdb1 pathway contributes to the maintenance of X chromosome inactivation[J]. Epigenetics Chromatin, 2014, 7:12. doi: 10.1186/1756-8935-7-12 pmid: 25028596
[62]	Gessaman JD, Selker EU. Induction of H3K9me3 and DNA methylation by tethered heterochromatin factors in Neurospora crassa[J]. PNAS, 2017, 114(45):E9598-E9607.
[63]	Chang YQ, Sun LD, Kokura K, et al. MPP₈ mediates the interactions between DNA methyltransferase Dnmt3a and H3K9 methyltransferase GLP/G9a[J]. Nat Commun, 2011, 2:533. doi: 10.1038/ncomms1549 URL

Lysine	H3 tail	H4 tail
K4	Set1,TRX,SET1A,SET1B,MLL1,MLL2,MLL3,MLL4,SMYD1,SMYD2,SMYD3,SET7/9,PRDM9	-
K9	Clr4,SU（VAR）3-9,G9a,SETDB1,ASH1,SUV39H1,SUV39H2,G9a,GLP,PRDM3,PRDM16	-
K27	EZH1,EZH2,G9A	-
K36	SET2,MES-4,SETD2,NSD1,NSD2,NSD3,SETD3,SMYD2,ASH1L,SETMAR,PRDM9	-
K79	DOT1L	-
K20	-	Set7,SET8,SET9,SUV4-20H1,SUV-20H2,SET9

Lysine	H3 tail	H4 tail
K4	Set1,TRX,SET1A,SET1B,MLL1,MLL2,MLL3,MLL4,SMYD1,SMYD2,SMYD3,SET7/9,PRDM9	-
K9	Clr4,SU（VAR）3-9,G9a,SETDB1,ASH1,SUV39H1,SUV39H2,G9a,GLP,PRDM3,PRDM16	-
K27	EZH1,EZH2,G9A	-
K36	SET2,MES-4,SETD2,NSD1,NSD2,NSD3,SETD3,SMYD2,ASH1L,SETMAR,PRDM9	-
K79	DOT1L	-
K20	-	Set7,SET8,SET9,SUV4-20H1,SUV-20H2,SET9