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Epigenome dynamics in regulation of germ cell fate via histone modification crosstalk

Research Project

Project/Area Number 17KK0185
Research Category

Fund for the Promotion of Joint International Research (Fostering Joint International Research)

Allocation TypeMulti-year Fund
Research Field General anatomy (including histology/embryology)
Research InstitutionTohoku University

Principal Investigator

MOCHIZUKI Kentaro  東北大学, 医学系研究科, 大学院非常勤講師 (20633499)

Project Period (FY) 2018 – 2021
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000)
Keywordsヒストン修飾 / DNAメチル化 / クロストーク / 生殖系列遺伝子 / 胚発生 / マウス / 生殖細胞 / エピジェネティクス / 始原生殖細胞 / エピブラスト / 多能性細胞 / エピゲノム
Outline of Final Research Achievements

Silencing of a subset of germline genes is dependent upon DNA methylation post-implantation. However, these genes are generally hypomethylated in the blastocyst, implicating alternative repressive pathways before implantation. Here, we show that in pre-implantation embryos, hypomethylated promoters of germline genes bound by PRC1.6 are enriched for RING1B-dependent H2AK119ub1 and H3K9me3. Accordingly, repression of these genes shows a greater dependence on PRC1.6 than DNA methylation. In contrast, germline genes are hypermethylated after implantation and their silencing is dependent upon SETDB1, PRC1.6/RING1B and DNA methylation, with H3K9me3. Thus, germline genes are initially repressed by PRC1.6, with DNA methylation subsequently engaged in post-implantation embryos.

Academic Significance and Societal Importance of the Research Achievements

生殖系列遺伝子の発生過程における早熟な発現は不妊の原因となることが示され、また、同遺伝子の体細胞系譜における異所的な発現は腫瘍形成のリスクとの関連が強く示唆されている。本研究の成果は、将来的に不妊や腫瘍形成の原因究明に役立ち、同時にPRC1.6複合体を標的とした予防手段・治療法確立の足がかりとなることが期待できる。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (5 results)

All 2021 2019 Other

All Int'l Joint Research (1 results) Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (2 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Remarks (1 results)

  • [Int'l Joint Research] The University of British Columbia(Canada)2019

    • Year and Date
      2019-05-01
    • Related Report
      2021 Annual Research Report
  • [Journal Article] Repression of germline genes by PRC1.6 and SETDB1 in the early embryo precedes DNA methylation-mediated silencing2021

    • Author(s)
      Mochizuki K, Sharif J, Shirane K, Uranishi K, Bogutz AB, Janssen SM, Suzuki A, Okuda A, Koseki H, Lorincz MC.
    • Journal Title

      Nature Communications

      Volume: 12(1) Issue: 1 Pages: 7020-7020

    • DOI

      10.1038/s41467-021-27345-x

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 初期胚におけるポリコムPRC1.6複合体およびSETDB1による生殖系列遺伝子群の抑制はDNAメチル化を介したサイレンシングに先行する2021

    • Author(s)
      望月研太郎
    • Organizer
      科学研究費新学術領域「非ゲノム情報複製」第12回Webinar
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Role of histone methylation, and its reader proteins in DNA methylation and silencing of germline genome-defense genes.2019

    • Author(s)
      Kentaro Mochizuki, Kevin Jeffers, Matthew C. Lorincz
    • Organizer
      The 6th Canadian Conference on Epigenetics
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Remarks] Epigenie(新着論文紹介)

    • URL

      https://epigenie.com/epigenetic-baby-steps-repress-germline-genome-defense-during-development/

    • Related Report
      2021 Annual Research Report

URL: 

Published: 2018-01-25   Modified: 2023-01-30  

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