早期胚胎DNA甲基化研究进展

doi:10.16431/j.cnki.1671-7236.2018.09.024

摘要/Abstract

摘要：

DNA甲基化修饰是研究最多的表观遗传修饰之一，在调控基因转录、染色体结构稳定、基因印迹、X染色体失活等方面发挥作用。尽管DNA甲基化是一种稳定的修饰，但其在个体发育进程中是动态变化的。目前，人们对早期胚胎发育中DNA甲基化修饰研究还不全面，随着全基因组DNA甲基化分析技术的进步，其在早期胚胎中的功能也逐渐揭示。作者主要论述了DNA甲基转移酶（DNMTs）的发现及其调控作用和DNA甲基化在早期胚胎中的作用。

关键词: DNA甲基化; 早期胚胎; DNA甲基转移酶; 表观遗传

Abstract:

DNA methylation is one of the most studied epigenetic,which plays a significant role in mediating biological progress such as gene regulation and expression,the stability of chromosome,genomic imprinting,X-chromosome inactivation.Although DNA methylation is stable,it is dynamic in the process of individual development.The function of DNA methylation modification in early embryonic developmental is not comprehensive.As the research into DNA methylation deepens,its function in pre-implantation embryos is also gradually revealed.This article mainly discusses the discovery and regulation of DNA methyltransferases (DNMTs) and the role of DNA methylation in pre-implantation embryos.

Key words: DNA methylation; pre-implantation embryos; DNA methytransferases; epigenetic

中图分类号:

Q954.4

王文娟, 岳媛, 安磊, 田见晖. 早期胚胎DNA甲基化研究进展[J]. 《中国畜牧兽医》, 2018, 45(9): 2531-2536.

WANG Wenjuan, YUE Yuan, AN Lei, TIAN Jianhui. Research Progress on DNA Methylation in Pre-implantation Embryo[J]. , 2018, 45(9): 2531-2536.

参考文献

[1] CHENG X,KUMAR S,POSFAI J,et al.Crystal structure of the HhaⅠ DNA methyltransferase complexed with S-adenosyl-L-methionine[J].Cell,1993,74(2):299-307.
[2] UYSAL F,OZTURK S,AKKOYUNLU G.DNMT1,DNMT3A and DNMT3B proteins are differently expressed in mouse oocytes and early embryos[J].Journal of Molecular Histology,2017,48(5-6):417-426.
[3] LI E,BESTOR T H,JAENISCH R.Targeted mutation of the DNA methyltransferase gene results in embryonic lethality[J].Cell,1992,69(6):915-926.
[4] OKANO M,BELL D W,HABER D A,et al.DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian develop-ment[J].Cell,1999,99(3):247-257.
[5] BOURC'HIS D,XU G L,LIN C S,et al.Dnmt3L and the establishment of maternal genomic imprints[J].Science,2001,294(5551):2536-2539.
[6] KANEDA M,OKANO M,HATA K,et al.Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting[J].Nature,2004,429(6994):900-903.
[7] BOSTICK M,KIM J K,ESTEVE P O,et al.UHRF1 plays a role in maintaining DNA methylation in mammalian cells[J].Science,2007,317(5845):1760-1764.
[8] MORGAN H D,SANTOS F,GREEN K,et al.Epigenetic reprogramming in mammals[J].Human Molecular Genetics,2005,14 Spec No 1:R47-58.
[9] BORGEL J,GUIBERT S,LI Y,et al.Targets and dynamics of promoter DNA methylation during early mouse development[J].Nature Genetics,2010,42(12):1093-1100.
[10] DUNWELL T L,HOLLAND P W H.A sister of NANOG regulates genes expressed in pre-implantation human development[J].Open Biology,2017,7(4):170027.
[11] MORGANI S M,BRICKMAN J M.LIF supports primitive endoderm expansion during pre-implantation development[J].Development,2015,142(20):3488-3499.
[12] KIMURA T,KAGA Y,SEKITA Y,et al.Pluripotent stem cells derived from mouse primordial germ cells by small molecule compounds[J].Stem Cells,2015,33(1):45-55.
[13] LENG L,TAN Y,GONG F,et al.Differentiation of primordial germ cells from induced pluripotent stem cells of primary ovarian insufficiency[J].Human Reproduction,2015,30(3):737-748.
[14] DEICHMANN U.Epigenetics:The origins and evolution of a fashionable topic[J].Developmental Biology,2016,416(1):249-254.
[15] RIGGS A D.X inactivation,differentiation,and DNA methylation[J].Cytogenetics and Cell Genetics,1975,14(1):9-25.
[16] HOLLIDAY R,PUGH J E.DNA modification mechanisms and gene activity during development[J].Science,1975,187(4173):226-232.
[17] WIGLER M,LEVY D,PERUCHO M.The somatic replication of DNA methylation[J].Cell,1981,24(1):33-40.
[18] BESTOR T,LAUDANO A,MATTALIANO R,et al.Cloning and sequencing of a cDNA encoding DNA methyltransferase of mouse cells.The carboxyl-terminal domain of the mammalian enzymes is related to bacterial restriction methyltransferases[J].Journal of Molecular Biology,1988,203(4):971-983.
[19] ARITA K,ARIYOSHI M,TOCHIO H,et al.Recognition of hemi-methylated DNA by the SRA protein UHRF1 by a base-flipping mechanism[J].Nature,2008,455(7214):818-821.
[20] MAENOHARA S,UNOKI M,TOH H,et al.Role of UHRF1 in de novo DNA methylation in oocytes and maintenance methylation in preimplantation embryos[J].PLoS Genetics,2017,13(10):e1007042.
[21] CHUANG L S,IAN H I,KOH T W,et al.Human DNA-(cytosine-5) methyltransferase-PCNA complex as a target for p21WAF1[J].Science,1997,277(5334):1996-2000.
[22] SPADA F,HAEMMER A,KUCH D,et al.DNMT1 but not its interaction with the replication machinery is required for maintenance of DNA methylation in human cells[J].The Journal of Cell Biology,2007,176(5):565-571.
[23] LEI H,OH S P,OKANO M,et al.De novo DNA cytosine methyltransferase activities in mouse embryonic stem cells[J].Development,1996,122(10):3195-3205.
[24] OKANO M,XIE S,LI E.Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases[J].Nature Genetics,1998,19(3):219-220.
[25] BARAU J,TEISSANDIER A,ZAMUDIO N,et al.The DNA methyltransferase DNMT3C protects male germ cells from transposon activity[J].Science,2016,354(6314):909-912.
[26] SMALLWOOD S A,KELSEY G.De novo DNA methylation:A germ cell perspective[J].Trends in Genetics,2012,28(1):33-42.
[27] LANE N,DEAN W,ERHARDT S,et al.Resistance of IAPs to methylation reprogramming may provide a mechanism for epigenetic inheritance in the mouse[J].Genesis,2003,35(2):88-93.
[28] SMITH Z D,CHAN M M,MIKKELSEN T S,et al.A unique regulatory phase of DNA methylation in the early mammalian embryo[J].Nature,2012,484(7394):339-344.
[29] BRANCO M R,KING M,PEREZ-GARCIA V,et al.Maternal DNA methylation regulates early trophoblast development[J].Developmental Cell,2016,36(2):152-163.
[30] CHEN T,ZHANG Y L,JIANG Y,et al.The DNA methylation events in normal and cloned rabbit embryos[J].FEBS Letters,2004,578(1-2):69-72.
[31] SHI W,DIRIM F,WOLF E,et al.Methylation reprogramming and chromosomal aneuploidy in in vivo fertilized and cloned rabbit preimplantation embryos[J].Biology of Reproduction,2004,71(1):340-347.
[32] DOBBS K B,RODRIGUEZ M,SUDANO M J,et al.Dynamics of DNA methylation during early development of the preimplantation bovine embryo[J].PLoS One,2013,8(6):e66230.
[33] BEAUJEAN N,TAYLOR J,GARDNER J,et al.Effect of limited DNA methylation reprogramming in the normal sheep embryo on somatic cell nuclear transfer[J].Biology of Reproduction,2004,71(1):185-193.
[34] HUAN Y,XIE B,LIU S,et al.A novel role for DNA methyltransferase 1 in regulating oocyte cytoplasmic maturation in pigs[J].PLoS One,2015,10(5):e0127512.
[35] FAN G,BEARD C,CHEN R Z,et al.DNA hypomethylation perturbs the function and survival of CNS neurons in postnatal animals[J].Journal of Neuroscience the Official Journal of the Society for Neuroscience,2001,21(3):788-797.
[36] KATO Y,KANEDA M,HATA K,et al.Role of the Dnmt3 family in de novo methylation of imprinted and repetitive sequences during male germ cell development in the mouse[J].Human Molecular Genetics,2007,16(19):2272-2280.
[37] WATANABE D,SUETAKE I,TADA T,et al.Stage-and cell-specific expression of Dnmt3a and Dnmt3b during embryogenesis[J].Mechanisms of Development,2002,118(1-2):187-190.
[38] LI W,SHUAI L,WAN H,et al.Androgenetic haploid embryonic stem cells produce live transgenic mice[J].Nature,2012,490(7420):407-411.
[39] YANG H,SHI L,WANG B A,et al.Generation of genetically modified mice by oocyte injection of androgenetic haploid embryonic stem cells[J].Cell,2012,149(3):605-617.
[40] HE W,ZHANG X,ZHANG Y,et al.Reduced self-diploidization and improved survival of semi-cloned mice produced from androgenetic haploid embryonic stem cells through overexpression of Dnmt3b[J].Stem Cell Reports,2018,10(2):477-493.
[41] LI Y,SEAH M K,O'NEILL C.Mapping global changes in nuclear cytosine base modifications in the early mouse embryo[J].Reproduction,2016,151(2):83-95.
[42] HIRASAWA R,SASAKI H.Dynamic transition of Dnmt3b expression in mouse pre-and early post-implantation embryos[J].Gene Expression Patterns,2009,9(1):27-30.
[43] WHYTE W A,BILODEAU S,ORLANDO D A,et al.Enhancer decommissioning by LSD1 during embryonic stem cell differentiation[J].Nature,2012,482(7384):221-225.
[44] JEDRUSIK A,COX A,WICHER K B,et al.Maternal-zygotic knockout reveals a critical role of Cdx2 in the morula to blastocyst transition[J].Developmental Biology,2015,398(2):147-152.
[45] JEDRUSIK A.Making the first decision:Lessons from the mouse[J].Reproductive Medicine and Biology,2015,14(4):135-150.
[46] COCKBURN K,ROSSANT J.Making the blastocyst:Lessons from the mouse[J].The Journal of Clinical Investigation,2010,120(4):995-1003.
[47] GARG V,MORGANI S,HADJANTONAKIS A K.Capturing identity and fate ex vivo:Stem cells from the mouse blastocyst[J].Current Topics in Developmental Biology,2016,120:361-400.
[48] TACHIBANA M,SPARMAN M,RAMSEY C,et al.Generation of chimeric rhesus monkeys[J].Cell,2012,148(1-2):285-295.
[49] MOLOTKOV A,MAZOT P,BREWER J R,et al.Distinct requirements for FGFR1 and FGFR2 in primitive endoderm development and exit from pluripotency[J].Developmental Cell,2017,41(5):511-526.
[50] FRUM T,HALBISEN M A,WANG C,et al.Oct4 cell-autonomously promotes primitive endoderm development in the mouse blastocyst[J].Developmental Cell,2013,25(6):610-622.
[51] ROODE M,BLAIR K,SNELL P,et al.Human hypoblast formation is not dependent on FGF signalling[J].Developmental Biology,2012,361(2):358-363.
[52] KIMBER S J,SNEDDON S F,BLOOR D J,et al.Expression of genes involved in early cell fate decisions in human embryos and their regulation by growth factors[J].Reproduction,2008,135(5):635-647.
[53] MOLKENTIN J D.The zinc finger-containing transcription factors GATA-4,-5,and -6.Ubiquitously expressed regulators of tissue-specific gene expression[J].The Journal of Biological Chemistry,2000,275(50):38949-38952.
[54] ODA M,KUMAKI Y,SHIGETA M,et al.DNA methylation restricts lineage-specific functions of transcription factor Gata4 during embryonic stem cell differentiation[J].PLoS Genetics,2013,9(6):e1003574.
[55] FENG Y,ZHAO L Z,HONG L,et al.Alteration in methylation pattern of GATA-4 promoter region in vitamin A-deficient offspring's heart[J].The Journal of Nutritional Biochemistry,2013,24(7):1373-1380.