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Uncovering the regulatory mechanism of meiotic entry in mammalian germ cells

Research Project

Project/Area Number 21K06843
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 48040:Medical biochemistry-related
Research InstitutionSaitama Medical University

Principal Investigator

Suzuki Ayumu  埼玉医科大学, 医学部, 講師 (80639708)

Co-Investigator(Kenkyū-buntansha) 奥田 晶彦  埼玉医科大学, 医学部, 教授 (60201993)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2023: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsMax / PRC1.6 / Myc / 減数分裂 / 生殖細胞 / 減数分裂の開始機構 / 体細胞分裂 / MYC / MGA
Outline of Research at the Start

本研究では、哺乳類生殖細胞においてMYC/MAXとMGA/MAXの両方の複合体が減数分裂の開始を制御するという仮説に基づいて以下の3点について研究を遂行する。
1. MAXの制御下で減数分裂の開始に関わる遺伝子の同定
2. 減数分裂の開始のために生殖細胞がPRC1.6の機能を破綻させる分子メカニズムの解明
3. 減数分裂開始におけるMYC/MAX転写複合体の機能低下の必要性の検討

Outline of Final Research Achievements

This study focused on the PRC1.6 complex, which includes MAX, and its role in regulating the transition from mitosis to meiosis in germ cells. We demonstrated that germ cell-specific knockout of MAX induces meiosis in both male and female primordial germ cells before sexual differentiation and found that MAX protein levels decrease significantly prior to meiotic initiation.
We worked on elucidating the control mechanism of meiotic initiation by MYC/MAX and MGA/MAX (PRC1.6) complexes, identifying a genomic region (MUR) involved in MAX expression regulation. These findings contribute to our understanding of the molecular basis of the mitosis-to-meiosis transition in germ cells and are expected to help clarify the causes of reproductive disorders. In the future, we aim to further elucidate the mechanisms of meiotic initiation and its disruption.

Academic Significance and Societal Importance of the Research Achievements

本研究は、MAXによる減数分裂遺伝子の抑制メカニズムの解明を通して、生殖細胞の運命決定や配偶子形成の基礎的理解を深めることを目的としている。この研究により、減数分裂開始の分子基盤が明らかになれば、体外での配偶子作成技術の向上や不妊症の新たな治療法の開発につながることが期待される。さらに近年、減数分裂遺伝子が腫瘍の発生や悪性化に関与していることが報告されているため、生体内での減数分裂遺伝子の抑制機構の理解は、がんの発生・悪性化のメカニズム解明にも役立つと考えられる。したがって将来的には、がんの予防法や治療法の進歩にも貢献できる可能性がある。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (13 results)

All 2024 2023 2022 2021

All Journal Article (5 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (8 results)

  • [Journal Article] MAX controls meiotic entry in sexually undifferentiated germ cells2024

    • Author(s)
      Suzuki A, Uranishi K, Nishimoto M, Mizuno Y, Mizuno S, Takahashi S, Eisenman RN, Okuda A.
    • Journal Title

      Scientific Reports

      Volume: 14(1) Issue: 1 Pages: 5236-5236

    • DOI

      10.1038/s41598-024-55506-7

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Alternative splicing for germ cell‐specific <i>Mga</i> transcript can be eliminated without compromising mouse viability or fertility2022

    • Author(s)
      Kitamura Yuka、Suzuki Ayumu、Uranishi Kousuke、Nishimoto Masazumi、Mizuno Seiya、Takahashi Satoru、Okuda Akihiko
    • Journal Title

      Development, Growth &amp; Differentiation

      Volume: 64 Issue: 7 Pages: 409-416

    • DOI

      10.1111/dgd.12806

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Two DNA binding domains of MGA act in combination to suppress ectopic activation of meiosis-related genes in mouse embryonic stem cells2021

    • Author(s)
      Uranishi K, Hirasaki M, Kitamura Y, Mizuno Y, Nishimoto M, Suzuki A, Okuda A.
    • Journal Title

      Stem Cells

      Volume: 39(11) Issue: 11 Pages: 1435-1446

    • DOI

      10.1002/stem.3433

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of germ cell-specific Mga variant mRNA that promotes meiosis via impediment of a non-canonical PRC12021

    • Author(s)
      Kitamura Y, Uranishi K, Hirasaki M, Nishimoto M, Suzuki A, Okuda A.
    • Journal Title

      Scientific Reports

      Volume: 11(1) Issue: 1 Pages: 9737-9737

    • DOI

      10.1038/s41598-021-89123-5

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] MAX は始原生殖細胞で減数分裂遺伝子を抑制する2024

    • Author(s)
      鈴木 歩
    • Organizer
      第3回有性生殖研究会「生殖の多様性」
    • Related Report
      2023 Annual Research Report
  • [Presentation] MgaはAtf7ipとSetdb1をリ クルートすることによって 減数分裂関連遺伝子に H3K9me3を導入する。2023

    • Author(s)
      浦西洸介, 鈴木歩, 平崎正孝, 西本正純, 奥田晶彦
    • Organizer
      第46回日本分子生物学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 減数分裂開始のためのポテンシャルの獲得とその発揮の制御2023

    • Author(s)
      鈴木歩, 浦西洸介, 北村友佳, 水野洋介, 西本正純, 望月健太郎, 水野聖哉, 高橋智, 奥田晶彦
    • Organizer
      第46回日本分子生物学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 減数分裂遺伝子の発現抑制はMaxにより制御される2022

    • Author(s)
      鈴木歩、浦西洸介、北村友佳、西本正純、水野聖哉、高橋智、奥田晶彦
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Research-status Report
  • [Presentation] Mga-Atf7ipの相互作用は減数分裂関連遺伝子領域の構造的ヘテロクロマチン化に寄与する2022

    • Author(s)
      浦西洸介、鈴木歩、平崎正孝、西本正純、奥田晶彦
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Research-status Report
  • [Presentation] Max regulates meiotic entry in mouse germ cells2021

    • Author(s)
      Ayumu Suzuki,Uranishi Kousuke, Kitamura Yuka, Nishimoto Masazumi, Akihiko Okuda
    • Organizer
      札幌国際がんシンポジウム
    • Related Report
      2021 Research-status Report
  • [Presentation] Mga inhibits meiotic initiation by regulating Meiosin-Stra8 signaling through the bHLHZ domain.2021

    • Author(s)
      Kousuke Uranishi, Yuka Kitamura, Ayumu Suzuki, Masataka Hirasaki, Masazumi Nishimoto, Akihiko Okuda
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Research-status Report
  • [Presentation] Molecular mechanisms for the initiation of meiosis in mouse germ cells2021

    • Author(s)
      Ayumu Suzuki, Kousuke Uranishi, Yuka Kitamura, Masazumi Nishimoto, Akihiko Okuda
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Research-status Report

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Published: 2021-04-28   Modified: 2025-01-30  

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