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Characterizing the roles of oocyte-specific factors in inhibiting unique features of the sperm epigenome

Research Project

Project/Area Number 22K15125
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 44020:Developmental biology-related
Research InstitutionOsaka University

Principal Investigator

SHIRANE Kenjiro  大阪大学, 大学院医学系研究科, 講師 (50855004)

Project Period (FY) 2022-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2023: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2022: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords卵母細胞 / エピゲノム性差 / DNAメチル化 / ヒストン修飾 / 転写制御因子 / 発生能獲得 / エピゲノム / 転写因子ネットワーク / 体外再構築系
Outline of Research at the Start

本研究では、雌雄の配偶子におけるゲノム機能の相互補完性を保証するメカニズムを明らかにする。配偶子は雌雄で異なるゲノム機能をもち、接合により相互補完されることにより発生能を獲得する。マウスをモデルとしたこれまでの研究は、性特異的なゲノムインプリントの確立機構の解明に注力されてきたが、雌雄の配偶子の相互補完性を保証する機構に着目したものは少ない。本研究では、生殖細胞の分化を再現する再構築系とゲノム網羅的な手法を用いて、卵子のゲノム機能の精子化を阻害する因子とその調節因子の同定を目指す。また、それらの摂動による発生能への影響を検証し、雌雄の配偶子が異なるゲノム機能を獲得する生物学的意義を考察する。

Outline of Final Research Achievements

This study aimed to elucidate the mechanism that prevents sperm-type epigenome in oocytes. To this end, we generated embryonic stem cells depleted of a candidate factor for this mechanism and reconstructed ovaries using these cells. Genome-wide DNA methylation analysis of mutant oocytes revealed that this factor is not involved in preventing sperm-type DNA methylation patterns in oocytes. Intriguingly, however, this factor is localized to the cytoplasm rather than the nucleus. This observation is particularly interesting, as typical epigenetic modifiers are active in the nucleus, suggesting a novel role for this factor in the cytoplasm of oocytes. In addition, we identified key transcription factors that activate this cytoplasmic factor in oocytes. In summary, we revealed transcriptional regulation of this factor and the role on the epigenetic regulation in oocytes. However, the role in the cytoplasm of oocytes warrants further investigation.

Academic Significance and Societal Importance of the Research Achievements

卵子と精子の持つ異なるエピゲノムパターンは個体の発生に必須であり、その分子基盤の解明は生物学的・医学的に大きな意義を持つ。本研究では、卵母細胞において精子型エピゲノム獲得を抑制する候補因子の一つに着目した。体外で卵母細胞の発生を再構築する実験系から、その発現制御機構の一端やその因子が直接的に卵母細胞のDNAメチル化パターンの形成に寄与しないことを明らかにした。加えて、この因子が細胞質に局在するという予想外の結果を得た。これは、卵母細胞が精子型のエピゲノム制御因子の機能を変化させる新たな機構の一つを示唆する。この因子の更なる解析は配偶子間の異なるゲノム機能の使い分けの理解につながると期待できる。

Report

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

    (8 results)

All 2023 2022 Other

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

  • [Int'l Joint Research] University of British Columbia(カナダ)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] Baylor College of Medicine(米国)

    • Related Report
      2023 Annual Research Report
  • [Journal Article] Epigenetic Mechanisms Governing Female and Male Germline Development in Mammals2023

    • Author(s)
      Shirane K and Lorincz M.
    • Journal Title

      Sexual Development

      Volume: 16 Issue: 5-6 Pages: 365-387

    • DOI

      10.1159/000529336

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ADAD2 functions in spermiogenesis and piRNA biogenesis in mice2023

    • Author(s)
      Lu Yonggang、Nagamori Ippei、Kobayashi Hisato、Kojima‐Kita Kanako、Shirane Kenjiro、Chang Hsin‐Yi、Nishimura Toru、Koyano Takayuki、Yu Zhifeng、Castaneda Julio M.、Matsuyama Makoto、Kuramochi‐Miyagawa Satomi、Matzuk Martin M.、Ikawa Masahito
    • Journal Title

      Andrology

      Volume: 11 Issue: 4 Pages: 698-709

    • DOI

      10.1111/andr.13400

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The DNMT3A ADD domain is required for efficient de novo DNA methylation and maternal imprinting in mouse oocytes2023

    • Author(s)
      Uehara Ryuji、Au Yeung Wan Kin、Toriyama Keisuke、Ohishi Hiroaki、Kubo Naoki、Toh Hidehiro、Suetake Isao、Shirane Kenjiro、Sasaki Hiroyuki
    • Journal Title

      PLOS Genetics

      Volume: 19 Issue: 8 Pages: e1010855-e1010855

    • DOI

      10.1371/journal.pgen.1010855

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The dynamic chromatin landscape and mechanisms of DNA methylation during mouse germ cell development2022

    • Author(s)
      Kenjiro Shirane
    • Journal Title

      Genes & Genetic Systems

      Volume: 97 Issue: 1 Pages: 3-14

    • DOI

      10.1266/ggs.21-00069

    • ISSN
      1341-7568, 1880-5779
    • Year and Date
      2022-02-01
    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dual role of <i>Ovol2</i> on the germ cell lineage segregation during gastrulation in mouse embryogenesis2022

    • Author(s)
      Naitou Yuki、Nagamatsu Go、Hamazaki Nobuhiko、Shirane Kenjiro、Hayashi Masafumi、Hayashi Makoto、Kobayashi Satoru、Hayashi Katsuhiko
    • Journal Title

      Development

      Volume: 149 Issue: 4 Pages: 1-13

    • DOI

      10.1242/dev.200319

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Defining the role of oocyte-inducing factors and their connective networks in oogenesis2023

    • Author(s)
      Kenjiro Shirane
    • Organizer
      2023 Germinal Stem Cell Biology, Gordon Research Conference
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited

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Published: 2022-04-19   Modified: 2025-01-30  

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