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Deciphering the roles of cohesin variants during mouse germline development

Research Project

Project/Area Number 21K20635
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0701:Biology at molecular to cellular levels, and related fields
Research InstitutionKyoto University

Principal Investigator

Nagano Masahiro  京都大学, 医学研究科, 助教 (00910663)

Project Period (FY) 2021-08-30 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsコヒーシン複合体 / 細胞分化 / 生殖細胞 / クロマチン高次構造 / auxin-inducible degron / AID / Hi-C / エピゲノム / Stag / コヒーシン / 生殖細胞試験管内再構成系 / クロマチン立体構造
Outline of Research at the Start

コヒーシンはクロマチン立体構造制御に重要であり、遺伝子発現制御に関わる。本研究では、生殖細胞試験管内再構成系を用い、コヒーシンバリアント(SA1-cohesin, SA2-cohesin)が行うクロマチン立体構造制御機構を解明し、生殖細胞分化過程におけるそれらの機能を解析する。本研究において、遺伝子発現を上流で制御するメカニズムであるクロマチン立体構造とエピゲノムを包括的に解析することで、普遍的なクロマチン立体構造制御のより精細な理解、さらには一部の白血病をはじめとしたコヒーシン異常による多くの疾患機序の解明にもつながることが期待される。

Outline of Final Research Achievements

The accurate understanding of chromatin architecture regulation by the cohesin complex is a critical challenge in biology, as the cohesin complex controls gene expression through chromatin structural organization. In this study, we focused on two variants of the somatic cohesin complex, SA1-cohesin and SA2-cohesin, and analyzed how they regulate germ cell differentiation. We observed an increased expression of SA2-cohesin and its enrichment at enhancers in the epiblast-like cells, which represent the state just before cell lineage determination. Further analysis using knockout cell lines revealed the crucial role of SA2-cohesin in determining germ cell fate.

Academic Significance and Societal Importance of the Research Achievements

コヒーシン複合体は遺伝子の働きを制御するためにクロマチンの形を整える役割を果たしています。本研究成果は生理学的な細胞分化という文脈において、クロマチンの構造がどのように変化していくかを解明するかを目的にしました。その結果、細胞分化の直前にはSA2-cohesinの量が増え、特定の場所で活発に働くことを発見しました。また、SA2-cohesinが欠損した細胞を調べた結果、生殖細胞への運命決定においてSA2-cohesinが重要な役割を果たすことが明らかになりました。これらの研究結果は、再生医療を含む細胞分化を必要とする分野において重要な知見となります。

Report

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

    (6 results)

All 2022 Other

All Int'l Joint Research (1 results) Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results) Presentation (3 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Funded Workshop (1 results)

  • [Int'l Joint Research] IMP(オーストリア)

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Nucleome programming is required for the foundation of totipotency in mammalian germline development2022

    • Author(s)
      Nagano Masahiro, Hu Bo, Yokobayashi Shihori et al.
    • Journal Title

      The EMBO Journal

      Volume: 41 Issue: 13

    • DOI

      10.15252/embj.2022110600

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Nucleome programming is required for the foundation of totipotency in mammalian germline development2022

    • Author(s)
      Nagano M, Hu B, Yokobayashi S, Saitou M.
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Nucleome programming for mammalian germ cell development.2022

    • Author(s)
      Nagano M
    • Organizer
      EMBO Japan Virtual Lectures, Molecular basis of epigenetic inheritance and totipotency
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Mitotic cohesin with Stag3 attenuates insulation in mouse spermatogonia.2022

    • Author(s)
      Nagano M
    • Organizer
      EMBO workshop, Nuclear structure and dynamics
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Funded Workshop] EMBO workshop2022

    • Related Report
      2022 Annual Research Report

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Published: 2021-10-22   Modified: 2024-01-30  

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