본문 바로가기
KERD
논문KCI 등재

히스톤 메틸화 변형을 통한 배아줄기세포의 후성 유전학적 조절

Epigenetic Regulation by Modification of Histone Methylation in Embryonic Stem Cells

김영은|박상규|박정아|이영희|하양화
한국발생생물학회 (The Korea Society Of Developmental Biology)|2011.12|발생과 생식 (DEVELOPMENT & REPRODUCTION)|제15권 제4호|pp. 273-279

2

조회

0

다운로드

1

인용

0

참고문헌

키워드

EpigeneticsActivationSuppressionEmbryonic stem cellsHistone methylationBivalency
주제분류생물학

초록

후성유전학적 조절은 DNA 서열상의 변화 없이도 유전자의 기능을 변화시킬 수 있는 현상을 뜻한다. 염색체의후성유전학적 상태는 히스톤 변형, DNA 변형 그리고 RNAi에 의한 유전자 침묵 등에 의해 조절된다. 본 총설에서는 배아줄기세포에서의 후성 유전학적 조절에 영향을 주는 요인으로서 히스톤(histone)의 메틸화에 초점을 맞추었다. 배아줄기세포에서 발현되는 유전자의 조절에는 두 가지 단백질 복합체가 관여한다. Polycomb repressive complex 2(PRC2)는 EED,EZH2, SUZ1를 주요인자로 포함하며, H3K27의 trimethylation(H3K27me3)을 증가시킴으로써 유전자의 발현을 억제한다. 이와는 대조적으로 Trithorax group(TrxG) 복합체는 주요인자로 MLL family를 포함하며, H3K4의 trimethylation(H3K4me3)시킴으로써 유전자의 발현을 활성화한다. PRC2 및 TrxG는 다양한 보조 단백질을 포함한다. 배아줄기세포에서 후성유전학적 조절의 두드러진 특징은 H3K27me3과 H3K4me3이 동시에 나타나는 이가 상태(bivalent state)이다. PRC2와 TrxG 복합체 그리고 H3K4나 K3K27의 메틸화에 특이적으로 작용하는 탈메틸효소(demethylase)가 한데 어우러져 배아줄기세포에서 만능성 관련 유전자와 발달 관련 유전자의 발현을 조절함으로써 줄기세포의 유지 및 분화에 기여한다. 따라서 후성유전학적 조절인자들에 대한 보다 자세한 연구는 배아줄기세포를 보다 잘 이해하고 활용하는데 도움을 줄 것이다

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 pluripotencyrelated 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.

참고문헌 (27)

  1. Ang YS, "WDR5 mediates self-renewal and reprogramming via the embryonic stem cell core transcriptional network", Cell, 145, pp.183~197 (2011)
  2. Boulay G, "Functional characterization of hPCL3 (human Polycomb-like 3) soforms identifies them as components of distinct EZH2 protein complexes", Biochem J, 434, pp.333~342 (2011)
  3. Chamberlain SJ, "Polycomb repressive complex 2 is dispensable for maintenance of embryonic stem cell pluripotency", Stem Cells, 26, pp.1496~1505 (2008)
  4. Chen X, "Integration of external signaling pathways with the core transcriptional network in embryonic stem cells", Cell, 133, pp.1106~1117 (2008)
  5. Christensen J, "RBP2 belongs to a family of demethylases, specific for tri-and dimethylated lysine 4 on histone 3", Cell, 128, pp.1063~1076 (2007)
  6. Christophersen NS, "Epigenetic control of embryonic stem cell fate", J Exp Med, 207, pp.2287~2295 (2007)
  7. Fouse SD, "Promoter CpG methylation contributes to ES cell gene regulation in parallel with Oct4", Nanog, PcG complex, and histone H3 K4, Cell Stem Cell, pp.2008, 2[DOI]
  8. Goldberg AD, "Epigenetics: A landscape takes shape", Cell, 128, pp.635~638 (2007)
  9. Grewal SI, "Heterochromatin and epigenetic control of gene expression", Science, 301, pp.798~802 (2003)
  10. Jiang H, "Role for DPY-30 in ES cell-fate specification by regulation of H3K4 methylation within bivalent domains", Cell, 144, pp.513~525 (2011)
  11. Yong Wook Jung, "Change of X Chromosome Status during Development and Reprogramming", 발생과 생식, 15(3), pp.187~195 (2011), 한국발생생물학회
  12. Kim D, "The role of PTIP in maintaining embryonic stem cell pluripotency", Stem Cells, 27, pp.1516~1523 (2009)
  13. Lim DA, "Chromatin remodelling factor MLL1 is essential for neurogenesis from postnatal neural stem cells", Nature, 458, pp.529~533 (2009)
  14. Lubitz S, "Increased apoptosis and skewed differentiation in mouse embryonic stem cells lacking the histone methyltransferase MLL2", Mol Biol Cell, 18, pp.2356~2366 (2007)
  15. Pan G, "Whole-genome analysis of histone H3 lysine 4 and lysine 27 methylation in human embryonic stem cells", Cell Stem Cell, 1, pp.299~312 (2007)
  16. Pasini D, "The polycomb group protein Suz12 is required for embryonic stem cell differentiation", Mol Cell Biol, 27, pp.3769~3779 (2007)
  17. Pasini D, "JARID2 regulates binding of the polycomb repressive complex 2 to target genes in ES cells", Nature, 464, pp.306~310 (2010)
  18. Pasini D, "Coordinated regulation of transcriptional repression by the RBP2 H3K4 demethylase and polycombrepressive complex 2", Genes Dev, 22, pp.1345~1355 (2008)
  19. Ringrose1 L, "Polycomb", Trithorax response elements and epigenetic memory of cell identity, 2007, pp.134, 223~232
  20. Schuettengruber B, "Recruitment of polycomb group complexes and their role in the dynamic regulation of cell fate choice", Development, 136, pp.3531~3542 (2009)
  21. 서유미, "줄기세포와 생식세포에서 리프로그래밍 인자에 대한 최근 연구 동향과 전망", 발생과 생식, 14(2), pp.43~50 (2010), 한국발생생물학회
  22. Shen X, "Jumonji modulates polycomb activity and self-renewal versus differentiation of stem cells", Cell, 139, pp.1303~1314 (2009)
  23. Shen X, "EZH1 mediates methylation on histone H3 lysine 27 and complements EZH2 in maintaining stem cell identity and executing pluripotency", Mol Cell, 32, pp.491~502 (2008)
  24. Stoller JZ, "Ash2l interacts with Tbx1 and is required during early embryogenesis", Exp Biol Med, 235, pp.569~576 (2010)
  25. Tate CM, "Cxxc finger protein 1 contains redundant functional domains that support embryonic stem cell cytosine methylation, histone methylation, and differentiation", Mol Cell Biol, 29, pp.3817~3831 (2009)
  26. Walker E, "PCL2 modulates gene regulatory networks controlling self-renewal and commitment in embryonic stem cells", Cell Cycle, 10, pp.45~51 (2011)
  27. Zhang Z, "PRC2 complexes with JARID2, MTF2, and esPRC2p48 in ES cells to modulate ES cell pluripotency and somatic cell reprograming", Stem Cells, 29, pp.229~240 (2011)

관련 논문AI추천

생쥐의 수정란 배아줄기세포와 체세포핵이식 배아줄기세포에서 각인유전자, H19, Igf2r, Snrpn의 메틸화 경향심성한, 이민호, 조율희, 주진영한국발생생물학회 · 발생과 생식2010 · 제14권 제4호The role of EZH1 and EZH2 in development and cancerChul-Hwan Lee, Hanbyeol Kim, Kyumin Park, Seounghyun Eum, Soo Hyun Lee, Yingying Li생화학분자생물학회 · BMB Reports2022 · 제55권 제12호Regulation and Role of EZH2 in CancerHirohito Yamaguchi, Mien-Chie Hung대한암학회 · Cancer Research and Treatment2014 · 제46권 제3호최근 보건의료분야에서 활발하게 연구되고 있는“Epigenetics”란 무엇인가? ―기본개념 및 기전을 중심으로―고성규, 김명동, 박성균, 신헌태, 이선동대한예방한의학회 · 대한예방한의학회지2010 · 제14권 제2호Epigenetic modification of retinoic acid-treated human embryonic stem cells김용성, 김혜민, 신형두, 정현섭, 한용만, Byung Lae Park, Han Chul Lee, Mi Jin Jang, Seun-Young Kim생화학분자생물학회 · BMB Reports2010 · 제43권 제12호Epigenetic reprogramming in mouse and human primordial germ cellsLee Sun-Min, Surani M. Azim생화학분자생물학회 · Experimental and Molecular Medicine2024 · 제56권

이 간행물의 다른 논문 (13건)

돼지 중간엽 줄기세포 동결에 있어서 동결보호제에 따른 특성 연구조재현, 노규진, 김미경, 박형준, 김충희pp. 281-289Association of Endometrial Polyps with Membranous Adhesions in Uterine CavityGun Ho Lee, Ji Young Kim, Yoon Jung Lee, Dong Hyun Cha, Jung Hyun Chopp. 291-299결빙억제제의 종류, 농도 및 침지시간이 참전복 Haliotis discus hannai 발생배의 생존활성에 미치는 영향정민환, 임한규, 손맹현, 정종균, 김종현, 장영진pp. 301-308Novel Single-Nucleotide Polymorphisms of SOHLH2 in Korean Patients with Premature Ovarian FailureHyun Ha Seok, Sang Woo Lyu, You Shin Kim, Seung Hoon Song, Hyung Jae Won, Mikyung Choi, Ji-hye Jeong, 심성한, 윤태기, 최영석, 김남근, Miree Parkpp. 309-313칡한우 혈액에서 DNA 다양성 분석을 통한 표지 유전자 탐색이호준, 윤종택, 홍연식, 김상환pp. 315-324
원문 보기