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Establishment of germline-specific epigenome in mouse spermatogenesis

Research Project

Project/Area Number 19K21196
Project/Area Number (Other) 18H06073 (2018)
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund (2019)
Single-year Grants (2018)
Review Section 0702:Biology at cellular to organismal levels, and related fields
Research InstitutionAzabu University

Principal Investigator

Maezawa So  麻布大学, 獣医学部, 講師 (90548174)

Project Period (FY) 2018-08-24 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords生殖細胞 / エピジェネティクス / クロマチン / エンハンサー / 精子形成 / A-MYB / 減数分裂 / エピゲノム / RNA-seq / ATAC-seq
Outline of Research at the Start

生殖細胞は生命の連続性を担う。生殖細胞が減数分裂期へ移行し進行する際には、大規模な遺伝子発現変化が伴うが、その分子機構には不明な点が多い。本研究では、精子形成期の減数分裂期移行に生じるエピゲノム変化やクロマチン構造変化を明らかにすることによって、減数分裂の開始・進行の分子機構を解明する。主な手法として、減数分裂期の対象のステージの生殖細胞を単離し、エピゲノムやクロマチン構造変化を、次世代シーケンサーを用いてゲノムワイドに、さらに細胞イメージング解析によって視覚的に解析する。また、モデル動物としてマウス及びブタを用いて比較解析を行うことにより、生物種特異的な制御機構に迫る。

Outline of Final Research Achievements

Due to bursts in the expression of thousands of germline-specific genes, the testis has the most diverse and complex transcriptome of all organs. Much of this unique gene expression takes place when mitotic germ cells differentiate to enter into meiotic prophase. Here, analyzing the male germline of mice, we demonstrate that the genome-wide reorganization of super enhancers (SEs) drives bursts of germline gene expression after the mitosis-to-meiosis transition. At the mitosis-to-meiosis transition, mitotic SEs resolve while meiotic SEs are established. Meiotic SEs are associated with the activation of key germline genes, thereby defining the cellular identity of germ cells. This SE switching is regulated by the establishment of meiotic SEs via A-MYB (MYBL1), a key transcription factor for germline genes. Prior to entry into meiosis, meiotic SEs are preprogrammed in mitotic spermatogonia, serving to ensure the unidirectional differentiation of spermatogenesis.

Academic Significance and Societal Importance of the Research Achievements

本研究では生殖細胞特異的な遺伝子発現を制御する活性化エンハンサーの動態を解明した。また、本研究によって新規に同定されたスーパーエンハンサーによって、精子形成期後期の分化進行に重要な遺伝子が制御されていることを見出した。さらに、A-MYB依存的なスーパーエンハンサーの形成機構を明らかにした。A-MYB依存的な生殖細胞特異的遺伝子発現は鳥類の精巣においても認められており、本研究で見出された分子機構は、進化的に保存された重要な精子形成遺伝子発現機構であると考えられる。本研究成果は、生体外での生殖細胞分化を制御する発生工学への応用や、ヒトの生殖医療の改善に役立つことが期待される。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • Research Products

    (8 results)

All 2020 2019 2018 Other

All Int'l Joint Research (1 results) Journal Article (2 results) (of which Int'l Joint Research: 2 results,  Open Access: 2 results) Presentation (5 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [Int'l Joint Research] シンシナティ小児病院医療センター(米国)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Super-enhancer switching drives a burst in germline gene expression at the mitosis-to-meiosis transition2020

    • Author(s)
      Maezawa So、Yukawa Masashi、Chen Xiaoting、Sakashita Akihiko、Alavattam Kris G.、Weirauch Matthew T.、Barski Artem、Namekawa Satoshi H.
    • Journal Title

      bioRxiv

      Volume: -

    • DOI

      10.1101/2020.03.11.987180

    • Related Report
      2019 Annual Research Report
    • Open Access / Int'l Joint Research
  • [Journal Article] Endogenous retroviruses drive species-specific germline transcriptomes in mammals2020

    • Author(s)
      Sakashita Akihiko、Maezawa So、Alavattam Kris G.、Yukawa Masashi、Barski Artem、Pavlicev Mihaela、Namekawa Satoshi H.
    • Journal Title

      bioRxiv

      Volume: -

    • DOI

      10.1101/2020.03.11.987230

    • Related Report
      2019 Annual Research Report
    • Open Access / Int'l Joint Research
  • [Presentation] Super-enhancer switching drives a burst in germline gene expression at the mitosis-to-meiosis transition2019

    • Author(s)
      前澤創
    • Organizer
      第13回エピジェネティクス 研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Super-enhancer switching drives a burst in germline gene expression at the mitosis-to-meiosis transition2019

    • Author(s)
      前澤創
    • Organizer
      EpiBio2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 生命の連続性に迫るー生殖細胞のエピゲノム形成機構2019

    • Author(s)
      前澤創
    • Organizer
      形態解析ワークショップー多様な顕微鏡を用いて
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] マウス精子形成期におけるクロマチン構造変化による遺伝子発現制御機構2018

    • Author(s)
      前澤創
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Genome-wide establishment of meiotic super-enhancers drives expression of spermatogenesis- specific genes2018

    • Author(s)
      前澤創
    • Organizer
      3R&3C Symposium 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research

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Published: 2018-08-27   Modified: 2024-03-26  

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