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Revision of the mechanism of action of the mammalian sex-determining gene Sry and its genome evolutionary process

Research Project

Project/Area Number 21H04769
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Review Section Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
Research InstitutionOsaka University

Principal Investigator

Tachibana Makoto  大阪大学, 大学院生命機能研究科, 教授 (80303915)

Co-Investigator(Kenkyū-buntansha) 宮脇 慎吾  岐阜大学, 応用生物科学部, 准教授 (70756759)
Project Period (FY) 2021-04-05 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥41,600,000 (Direct Cost: ¥32,000,000、Indirect Cost: ¥9,600,000)
Fiscal Year 2023: ¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000)
Fiscal Year 2022: ¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000)
Fiscal Year 2021: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Keywords性決定 / Sry / 性決定遺伝子 / ゲノム進化 / 相互作用因子 / 性決定因子 / タンパク質分解
Outline of Research at the Start

性分化は有性生殖をおこなう生物に必須の生命現象である。ほ乳類では、性決定遺伝子Sryによって性的に未分化な生殖腺がオス化する。私たちは、マウスSryにこれまで未同定だった第2エキソンが存在しており、それが新規性決定因子SRY-Tをコードしていることを明らかにした。(宮脇と立花ら、Science 2020)。本研究では、SRY-Tの機能をさらに追及しつつ、Sry遺伝子の進化の謎も明らかにする。

Outline of Final Research Achievements

In mammals, the sex-determining gene Sry is transiently expressed in the fetal gonads, testiculating sexually undifferentiated gonads. We found that the sex-determining gene Sry in mice has a previously unidentified second exon, which encodes the true sex determinant SRY-T. We will revise the mammalian sex determination mechanism by understanding the mechanism of action of the true sex determinant SRY-T, rather than previous results obtained from known SRY (SRY-S).

Academic Significance and Societal Importance of the Research Achievements

ほ乳類の生殖腺オルガノイド構築の技術は、我が国が世界を先導している。本研究提案は、このような我が国の強みをより一層強化する可能性を秘めている。すなわち、これまでのSRY-Sによって構築されてきた性決定の分子機序を一新し、実際に生体内で働いている真の性決定因子SRY-Tの分子機序を明らかにすることは、オス化生殖腺(精巣)のオルガノイドの作製をより効率化するための礎を提供する。また、ヒトの性分化疾患の原因究明にもつながる。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Comments on the Screening Results   Annual Research Report
  • Research Products

    (35 results)

All 2024 2023 2022 2021 Other

All Int'l Joint Research (3 results) Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 4 results) Presentation (13 results) (of which Int'l Joint Research: 6 results,  Invited: 10 results) Book (5 results) Remarks (5 results) Funded Workshop (1 results)

  • [Int'l Joint Research] Qeensland University(オーストラリア)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] クイーンズランド大学(オーストリア)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] カリフォルニア大学デービス校(米国)

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Epigenetic modifier G9a is involved in regulation of mouse tongue development2024

    • Author(s)
      Ideno Hisashi、Nakashima Kazuhisa、Komatsu Koichiro、Kimura Hiroshi、Shinkai Yoichi、Tachibana Makoto、Nifuji Akira
    • Journal Title

      Journal of Oral Biosciences

      Volume: 66 Issue: 1 Pages: 35-40

    • DOI

      10.1016/j.job.2023.12.007

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CDYL reinforces male gonadal sex determination through epigenetically repressing <i>Wnt4</i> transcription in mice2023

    • Author(s)
      Okashita Naoki、Maeda Ryo、Tachibana Makoto
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 120 Issue: 20

    • DOI

      10.1073/pnas.2221499120

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] HP1 maintains protein stability of H3K9 methyltransferases and demethylases2022

    • Author(s)
      Ryo Maeda, Makoto Tachibana
    • Journal Title

      EMBO Reports

      Volume: 23 Issue: 4

    • DOI

      10.15252/embr.202153581

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] マウス性決定遺伝子Sryの「隠れたエキソン」の発見2022

    • Author(s)
      立花誠
    • Journal Title

      ファルマシア

      Volume: 58 Pages: 34-38

    • NAID

      130008138918

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Dynamic erectile responses of a novel penile organ model utilizing TPEM.2021

    • Author(s)
      Hashimoto D, Hirashima T, Yamamura H, Kataoka T, Fujimoto K, Hyuga T, Yoshiki A, Kimura K, Kuroki S, Tachibana M, Suzuki K, Yamamoto N, Morioka S, Sasaki T, Yamada G.
    • Journal Title

      Biol Reprod.

      Volume: in press Issue: 4 Pages: 875-886

    • DOI

      10.1093/biolre/ioab011

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Meiosis-specific ZFP541 repressor complex promotes developmental progression of meiotic prophase towards completion during mouse spermatogenesis2021

    • Author(s)
      Horisawa-Takada Yuki et al.
    • Journal Title

      Nature Communications

      Volume: 12 Issue: 1 Pages: 3184-3184

    • DOI

      10.1038/s41467-021-23378-4

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Generation of ovarian follicles from mouse pluripotent stem cells2021

    • Author(s)
      Yoshino Takashi、Suzuki Takahiro、Nagamatsu Go、Yabukami Haruka、Ikegaya Mika、Kishima Mami、Kita Haruka、Imamura Takuya、Nakashima Kinichi、Nishinakamura Ryuichi、Tachibana Makoto、Inoue Miki、Shima Yuichi、Morohashi Ken-ichirou、Hayashi Katsuhiko
    • Journal Title

      Science

      Volume: 373 Issue: 6552 Pages: 282-289

    • DOI

      10.1126/science.abe0237

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 性決定遺伝子の全貌-マウスSryにおける“隠れエキソン”の発見-2021

    • Author(s)
      宮脇慎吾、立花誠
    • Journal Title

      医学のあゆみ

      Volume: 278 Pages: 1132-1133

    • Related Report
      2021 Annual Research Report
  • [Presentation] ほ乳類性決定におけるエピジェネティック制御の役割2024

    • Author(s)
      立花誠
    • Organizer
      第4回 有性生殖研究会「未来にむけた生殖研究」
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] CDYL reinforces male gonadal sex determination through epigenetically repressing Wnt4 transcription in mice2023

    • Author(s)
      Makoto Tachibana
    • Organizer
      9th International Symposium on the Biology of Vertebrate Sex Determination
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ほ乳類性決定におけるエピジェネティック制御の役割2023

    • Author(s)
      立花誠
    • Organizer
      第16回日本エピジェネティクス研究会年会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] CDYL reinforces male gonadal sex determination through epigenetically repressing Wnt4 transcription in mice2023

    • Author(s)
      Makoto Tachibana
    • Organizer
      9th International Conference of Brain and Gonadal Biology
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ほ乳類の性が決まるしくみとエピジェネティクス2023

    • Author(s)
      立花誠
    • Organizer
      第39回 西宮市ライフサイエンスセミナー
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] マウス性決定のエピジェネティック制御機構2023

    • Author(s)
      立花誠
    • Organizer
      日本遺伝学会第95回年会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] The Mouse Sry Locus Harbors a Cryptic Exon that is Essential for Male Sex Determination2022

    • Author(s)
      Makoto Tachibana
    • Organizer
      The 12th Biennial Scientific Meeting of the Asia Pacific Paediatric Endocrine Siciety 2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] H3K9me2/3 represses the expression of 2-cell-stage-specific genes in mESCs2022

    • Author(s)
      前田亮、立花誠
    • Organizer
      第95回日本生化学会大会シンポジウム
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] HP1 maintains protein stability of H3K9 methyltransferases in mammalian cells2022

    • Author(s)
      Makoto Tachibana
    • Organizer
      第95回日本生化学会大会シンポジウム
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Role of iron metabolism in mouse sex determination2022

    • Author(s)
      Makoto Tachibana
    • Organizer
      第45回日本分子生物学会シンポジウム
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] マウスES細胞におけるトランスポゾンの抑制機構2021

    • Author(s)
      立花 誠
    • Organizer
      転移因子研究会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Epigenetic regulation of two-cell-specific genes in mouse ES cells2021

    • Author(s)
      立花 誠
    • Organizer
      日本分子生物学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] HP1-dependent heterochromatin formation in mammalian cells2021

    • Author(s)
      Ryo Maeda, Makoto Tachibana
    • Organizer
      染色体ワークショップ
    • Related Report
      2021 Annual Research Report
  • [Book] 「隠れていた真のマウス性決定因子SRY-Tの発見」2024

    • Author(s)
      立花誠
    • Total Pages
      4
    • Publisher
      ニューサイエンス社
    • Related Report
      2023 Annual Research Report
  • [Book] 総論「連続する表現型として性を再定義する」2024

    • Author(s)
      立花誠
    • Total Pages
      2
    • Publisher
      ニューサイエンス社
    • Related Report
      2023 Annual Research Report
  • [Book] Spectrum of Sex: The Molecular Bases that Induce Various Sexual Phenotypes2023

    • Author(s)
      Minoru Tanaka and Makoto Tachibana
    • Total Pages
      233
    • Publisher
      Springer Nature
    • Related Report
      2023 Annual Research Report 2022 Annual Research Report
  • [Book] The Evolutionary Aspects of the Mammalian Sex-Determining Gene SRY.2023

    • Author(s)
      Shingo Miyawaki and Makoto Tachibana
    • Total Pages
      17
    • Publisher
      Springer Nature
    • Related Report
      2023 Annual Research Report
  • [Book] The Evolutionary Aspects of the Mammalian Sex-Determining Gene SRY2023

    • Author(s)
      Shingo Miyawaki and Makoto Tachibana
    • Total Pages
      17
    • Publisher
      Springer Nature
    • Related Report
      2022 Annual Research Report
  • [Remarks] 大阪大学生命機能研究科立花研HP

    • URL

      https://tachibana-lab.net/

    • Related Report
      2023 Annual Research Report
  • [Remarks] 新学術領域研究「性スペクトラム」HP

    • URL

      https://park.itc.u-tokyo.ac.jp/sexspectrum/

    • Related Report
      2023 Annual Research Report
  • [Remarks] 大阪大学大学院生命機能研究科 立花研究室

    • URL

      https://tachibana-lab.net/

    • Related Report
      2022 Annual Research Report
  • [Remarks] 性スペクトラムー連続する表現型としての雌雄ー

    • URL

      http://park.itc.u-tokyo.ac.jp/sexspectrum/index.html

    • Related Report
      2021 Annual Research Report
  • [Remarks] 大阪大学大学院生命機能研究科 立花研究室

    • URL

      https://tachibana-lab.net/

    • Related Report
      2021 Annual Research Report
  • [Funded Workshop] 第45回日本分子生物学会シンポジウム「Role of epigenetic regulation in mammalian health and disease」2022

    • Related Report
      2022 Annual Research Report

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

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