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Regulation of preimplantation embryonic fate and plasticity by the PRC1 Polycomb group complex

Research Project

Project/Area Number 16K07372
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Developmental biology
Research InstitutionKumamoto University

Principal Investigator

Endoh Mitsuhiro  熊本大学, 発生医学研究所, 助教 (40391883)

Co-Investigator(Kenkyū-buntansha) 須田 年生  熊本大学, 国際先端医学研究機構, 卓越教授 (60118453)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsエピジェネティクス / 発生 / 哺乳類 / 多能性幹細胞 / 転写 / 細胞分化 / 生殖 / 減数分裂 / ヒストン修飾 / 初期発生 / リプログラミング / 生殖細胞 / クロマチン / ポリコーム / 初期胚 / 転写因子 / 幹細胞 / 発現制御 / 分化
Outline of Final Research Achievements

PCGF6 (polycomb group ring finger 6) interacts with RING1A/B and E2F6 associated factors to form a non-canonical PRC1 (polycomb repressive complex 1) known as PCGF6-PRC1. Here, we demonstrate that PCGF6-PRC1 plays a role in repressing a subset of PRC1 target genes by recruiting RING1B and mediating downstream mono-ubiquitination of histone H2A. PCGF6-PRC1 bound loci are highly enriched for promoters of germ cell-related genes in mouse embryonic stem cells (ESCs). Conditional ablation of Pcgf6 in ESCs leads to robust de-repression of such germ cell-related genes, in turn affecting cell growth and viability. We also find a role for PCGF6 in pre- and peri-implantation mouse embryonic development. We further show that a heterodimer of the transcription factors MAX and MGA recruits PCGF6 to target loci. PCGF6 thus links sequence specific target recognition by the MAX/MGA complex to PRC1-dependent transcriptional silencing of germ cell-specific genes in pluripotent stem cells.

Academic Significance and Societal Importance of the Research Achievements

ポリコーム群PRC1.6が他のPRC1とは異なり転写因子Mga/Maxに依存して標的遺伝子を認識すること、生殖関連遺伝子群および2細胞胚遺伝子群の新規エピジェネティック制御機構であることが明らかになった。グローバルなDNA脱メチル化を受けるナイーブ型の多能性幹細胞に特有のエピジェネティック機構であると考えられ、初期発生やエピジェネティックリプログラミングの分子基盤の理解に繋がる重要な発見と言える。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (12 results)

All 2018 2017 2016 Other

All Int'l Joint Research (3 results) Journal Article (4 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 4 results,  Open Access: 4 results,  Acknowledgement Compliant: 1 results) Presentation (5 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results)

  • [Int'l Joint Research] シンガポール国立大学がん科学研究所(シンガポール)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Cancer Science Institute of Singapore(Singapore)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] Cancer Science Institute of Singapore(シンガポール)

    • Related Report
      2016 Research-status Report
  • [Journal Article] Folliculin Regulates Osteoclastogenesis Through Metabolic Regulation2018

    • Author(s)
      3.Baba M, Endoh M, Ma W, Toyama H, Hirayama A, Nishikawa K, Takubo K, Hano H, Hasumi H, Umemoto T, Hashimoto M, Irie N, Esumi C, Kataoka M, Nakagata N, Soga T, Yao M, Kamba T, Minami T, Ishii M, and Suda T.
    • Journal Title

      Journal of Bone and Mineral Research

      Volume: 33 Issue: 10 Pages: 1785-1798

    • DOI

      10.1002/jbmr.3477

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] FANTOM5 CAGE profiles of human and mouse samples2017

    • Author(s)
      Noguchi Shuhei、Arakawa Takahiro、Ogishima Soichi、ほか
    • Journal Title

      Sci Data

      Volume: 4 Issue: 1 Pages: 170112-170112

    • DOI

      10.1038/sdata.2017.112

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] PCGF6-PRC1 suppresses premature differentiation of mouse embryonic stem cells by regulating germ cell-related genes.2017

    • Author(s)
      Endoh M, Endo TA, Shinga J, Hayashi K, Farcas A, Ma KW, Ito S, Sharif J, Endoh T, Onaga N, Nakayama M, Ishikura T, Masui O, Kessler BM, Suda T, Ohara O, Okuda A, Klose RJ, Koseki H.
    • Journal Title

      Elife

      Volume: 6 Pages: 27970-27970

    • DOI

      10.7554/elife.21064

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Conversion of T cells to B cells by inactivation of polycomb-mediated epigenetic suppression of the B-lineage program.2016

    • Author(s)
      Ikawa T, Masuda K, Endo TA, Endo M, Isono K, Koseki Y, Nakagawa R, Kometani K, Takano J, Agata Y, Katsura Y, Kurosaki T, Vidal M, Koseki H, Kawamoto H.
    • Journal Title

      Genes. Dev.

      Volume: 30 Issue: 22 Pages: 2475-2485

    • DOI

      10.1101/gad.290593.116

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] FLCN-TFE3 Feedback Loop Prevents Lysosomal Storage and BHD Tumorigenesis2018

    • Author(s)
      Mitsuhiro Endoh, Masaya Baba, Tamie Endoh, Ayako Ishizu, Toshio Suda
    • Organizer
      FRONTIERS IN CANCER SCIENCE 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ポリコーム群遺伝子Pcgf6による生殖細胞特異的遺伝子の発現および胚発生の制御2017

    • Author(s)
      遠藤 充浩
    • Organizer
      千葉大学大学院医学研究院
    • Place of Presentation
      千葉大学大学院医学研究院
    • Year and Date
      2017-03-31
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] The FLCN-TFE3 axis regulates macrophage activation through cellular metabolism2017

    • Author(s)
      Mitsuhiro Endoh, Masaya Baba, Yong-Mei Guo, Terumasa Umemoto, Michihiro Hashimoto, Naoto Takahashi, Ken-ichi Sawada, Laura S. Schmidt, Toshio Suda
    • Organizer
      International Society for Experimental Hematology (ISEH) 46th Annual Scientific Meeting
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Loss of FLCN induces activation of hemophagocytic macrophages through the GABARAP-associated autophagy-lysosome process2017

    • Author(s)
      Mitsuhiro Endoh, Masaya Baba, Tamie Endoh, Yang Chong, Toshio Suda
    • Organizer
      Frontiers in Cancer Science (FCS) 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] ポリコーム群 PCGF6-PRC1複合体は生殖細胞系列遺伝子の抑制を介して胚性幹細胞の未熟な分化を抑制する2016

    • Author(s)
      遠藤 充浩、遠藤 高帆、林 克彦、須田 年生、古関 明彦
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-12-01
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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