Browse > Article

Epigenetic Regulation by Modification of Histone Methylation in Embryonic Stem Cells  

Ha, Yang-Hwa (Dept. of Biochemistry, College of Natural Sciences, Chungbuk National University)
Kim, Young-Eun (Dept. of Biochemistry, College of Natural Sciences, Chungbuk National University)
Park, Jeong-A (Dept. of Biochemistry, College of Natural Sciences, Chungbuk National University)
Park, Sang-Kyu (Dept. of Biochemistry, College of Natural Sciences, Chungbuk National University)
Lee, Young-Hee (Dept. of Biochemistry, College of Natural Sciences, Chungbuk National University)
Publication Information
Development and Reproduction / v.15, no.4, 2011 , pp. 273-279 More about this Journal
Abstract
Epigenetic regulation is a phenomenon that changes the gene function without changing the underlying DNA sequences. Epigenetic status of chromosome is regulated by mechanisms such as histone modification, DNA modification, and RNAi silencing. In this review, we focused on histone methylation for epigenetic regulation in ES cells. Two antagonizing multiprotein complexes regulate methylation of histones to guide expression of genes in ES cells. The Polycomb repressive complex 2 (PRC2), including EED, EZH2, and SUZ12 as core factors, contributes to gene repression by increasing trimethylation of H3K27 (H3K27me3). In contrast, the Trithorax group (TrxG) complex including MLL is related to gene activation by making H3K4me3. PRC2 and TrxG accompany a variety of accessory proteins. Most prominent feature of epigenetic regulation in ES cells is a bivalent state in which H3K27me3 and H3K4me3 appear simultaneously. Concerted regulation of PRC2, TrxG complex, and H3K4- or H3K27-specific demethylases activate expression of pluripotency-related genes and suppress development-related genes in ES cells. Modified balance of the regulators also enables ES cells to efficiently differentiate to a variety of cells upon differentiating signals. More detailed insights on the epigenetic regulators and their action will lead us to better understanding and use of ES cells for future application.
Keywords
Epigenetics; Histone methylation; Embryonic stem cells; Activation; Suppression; Bivalency;
Citations & Related Records
Times Cited By KSCI : 2  (Citation Analysis)
연도 인용수 순위
1 Shen X, Kim W, Fujiwara Y, Simon MD, Liu Y, Mysliwiec MR, Yuan GC, Lee Y, Orkin SH (2009) Jumonji modulates polycomb activity and self-renewal versus differentiation of stem cells. Cell 139:1303-1314.   DOI   ScienceOn
2 Shen X, Liu Y, Hsu YJ, Fujiwara Y, Kim J, Mao X, Yuan GC, Orkin SH (2008) EZH1 mediates methylation on histone H3 lysine 27 and complements EZH2 in maintaining stem cell identity and executing pluripotency. Mol Cell 32:491-502.   DOI   ScienceOn
3 Stoller JZ, Huang L, Tan CC, Huang F, Zhou DD, Yang J, Gelb BD, Epstein JA (2010) Ash2l interacts with Tbx1 and is required during early embryogenesis. Exp Biol Med 235:569-576.   DOI   ScienceOn
4 Tate CM, Lee JH, Skalnik DG (2009) Cxxc finger protein 1 contains redundant functional domains that support embryonic stem cell cytosine methylation, histone methylation, and differentiation. Mol Cell Biol 29:3817-3831.   DOI   ScienceOn
5 Walker E, Manias JL, Chang1 WY, Stanford WL (2011) PCL2 modulates gene regulatory networks controlling self-renewal and commitment in embryonic stem cells. Cell Cycle 10:45-51.   DOI   ScienceOn
6 Zhang Z, Jones A, Sun CW, Li C, Chang CW, Joo HY, Dai Q, Mysliwiec MR, Wu LC, Guo Y, Yang W, Liu K, Pawlik KM, Erdjument-Bromage H, Tempst P, Lee Y, Min J, Townes TM, Wang H (2011) PRC2 complexes with JARID2, MTF2, and esPRC2p48 in ES cells to modulate ES cell pluripotency and somatic cell reprograming. Stem Cells 29:229-240.   DOI   ScienceOn
7 Jiang H, Shukla A, Wang X, Chen WY, Bernstein BE, Roeder RG (2011) Role for DPY-30 in ES cell-fate specification by regulation of H3K4 methylation within bivalent domains. Cell 144:513-525.   DOI   ScienceOn
8 Jung YW, Park IH (2011) Change of X chromosome status during development and reprogramming. Dev Reprod 15:187-195.
9 Lim DA, Huang YC, Swigut T, Mirick AL, Garcia-Verdugo JM, Wysocka J, Ernst P, Alvarez-Buylla A (2009) Chromatin remodelling factor MLL1 is essential for neurogenesis from postnatal neural stem cells. Nature 458:529-533.   DOI   ScienceOn
10 Kim D, Patel SR, Xiao H, Dressler GR (2009) The role of PTIP in maintaining embryonic stem cell pluripotency. Stem Cells 27:1516-1523.   DOI   ScienceOn
11 Lubitz S, Glaser S, Schaft J, Stewart AF, Anastassiadis K (2007) Increased apoptosis and skewed differentiation in mouse embryonic stem cells lacking the histone methyltransferase MLL2. Mol Biol Cell 18:2356-2366.   DOI   ScienceOn
12 Pan G, Tian S, Nie J, Yang C, Ruotti V, Wei H, Jonsdottir GA, Stewart R, Thomson JA (2007) Whole-genome analysis of histone H3 lysine 4 and lysine 27 methylation in human embryonic stem cells. Cell Stem Cell 1:299-312.   DOI   ScienceOn
13 Pasini D, Bracken AP, Hansen JB, Capillo M, Helin K (2007) The polycomb group protein Suz12 is required for embryonic stem cell differentiation. Mol Cell Biol 27:3769-3779.   DOI   ScienceOn
14 Pasini D, Cloos PA, Walfridsson J, Olsson L, Bukowski JP, Johansen JV, Bak M, Tommerup N, Rappsilber J, Helin K (2010) JARID2 regulates binding of the polycomb repressive complex 2 to target genes in ES cells. Nature 464:306-310.   DOI   ScienceOn
15 Pasini D, Hansen KH, Christensen J, Agger K, Cloos PA, Helin K (2008) Coordinated regulation of transcriptional repression by the RBP2 H3K4 demethylase and polycombrepressive complex 2. Genes Dev 22:1345-1355.   DOI   ScienceOn
16 Ringrose1 L, Paro R (2007) Polycomb/Trithorax response elements and epigenetic memory of cell identity. Development 134:223-232.   DOI   ScienceOn
17 Schuettengruber B, Cavalli G (2009) Recruitment of polycomb group complexes and their role in the dynamic regulation of cell fate choice. Development 136:3531-3542.   DOI   ScienceOn
18 Seo Y-M, Lee K-A (2010) Current progress and prospects of reprogramming factors - stem cells vs germ cells. Dev Reprod 14:43-50.
19 Boulay G, Rosnoblet C, Guerardel C, Angrand PO, Leprince D (2011) Functional characterization of hPCL3 (human Polycomb-like 3) soforms identifies them as components of distinct EZH2 protein complexes. Biochem J 434:333-342.   DOI   ScienceOn
20 Ang YS, Tsai SY, Lee DF, Monk J, Su J, Ratnakumar K, Ding J, Ge Y, Darr H, Chang B, Wang J, Rendl M, Bernstein E, Schaniel C, Lemischka IR (2011) WDR5 mediates self-renewal and reprogramming via the embryonic stem cell core transcriptional network. Cell 145:183-197.   DOI   ScienceOn
21 Chamberlain SJ, Yee D, Magnuson T (2008) Polycomb repressive complex 2 is dispensable for maintenance of embryonic stem cell pluripotency. Stem Cells 26:1496-1505.   DOI   ScienceOn
22 Chen X, Xu H, Yuan P, Fang F, Huss M, Vega VB, Wong E, Orlov YL, Zhang W, Jiang J, Loh YH, Yeo HC, Yeo ZX, Narang V, Govindarajan KR, Leong B, Shahab A, Ruan Y, Bourque G, Sung WK, Clarke ND, Wei CL, Ng HH (2008) Integration of external signaling pathways with the core transcriptional network in embryonic stem cells. Cell 133:1106-1117.   DOI   ScienceOn
23 Christensen J, Agger K, Cloos PA, Pasini D, Rose S, Sennels L, Rappsilber J, Hansen KH, Salcini AE, Helin K (2007) RBP2 belongs to a family of demethylases, specific for tri-and dimethylated lysine 4 on histone 3. Cell 128:1063-1076.   DOI   ScienceOn
24 Christophersen NS, Helin K (2007) Epigenetic control of embryonic stem cell fate. J Exp Med 207:2287-2295.
25 Fouse SD, Shen Y, Pellegrini M, Cole S, Meissner A, Van Neste L, Jaenisch R, Fan G (2008) Promoter CpG methylation contributes to ES cell gene regulation in parallel with Oct4/Nanog, PcG complex, and histone H3 K4/K27 trimethylation. Cell Stem Cell 2:160-169.   DOI   ScienceOn
26 Goldberg AD, Allis CD, Bernstein E (2007) Epigenetics: A landscape takes shape. Cell 128:635-638.   DOI   ScienceOn
27 Grewal SI, Moazed D (2003) Heterochromatin and epigenetic control of gene expression. Science 301:798-802.   DOI   ScienceOn