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Evolution of mammalian sex-determining system by insertion of transposons

Research Project

Project/Area Number 19K22388
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

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

Principal Investigator

Tachibna Makoto  大阪大学, 生命機能研究科, 教授 (80303915)

Project Period (FY) 2019-06-28 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2019: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords性決定遺伝子 / トランスポゾン / 性決定 / Y染色体
Outline of Research at the Start

申請者は、ほ乳類性決定遺伝子であるSryの近傍に、トランスポゾン様の配列が二つ(SrxとSrz)が存在することを見いだした。これらのトランスポゾン配列の欠損マウスを作製し、マウスのオス化との関わりについて検証する。さらに、部分変異の導入によりこれらのトランスポゾンのどの配列がオス化に重要なのかを明らかにする。

Outline of Final Research Achievements

The mammalian sex-determining gene Sry induces male development. Since its discovery 30 years ago, Sry has been believed to be a single-exon gene. Here, we identified a cryptic second exon of mouse Sry and a corresponding novel transcript, two-exon Sry (Sry-T). XY mice lacking Sry-T were sex-reversed, and ectopic expression of Sry-T in XX mice induced male development. Sry-T mRNA is expressed similarly to that of canonical single-exon Sry (Sry-S), but SRY-T protein is expressed predominantly, due to the absence of a degron which we identified in the C-terminus of SRY-S. Sry exon2 appears to have evolved recently in mice, through acquisition of retrotransposon-derived coding sequence to replace the degron. Our findings suggest that in nature, SRY-T, not SRY-S, is the bona fide testis-determining factor.

Academic Significance and Societal Importance of the Research Achievements

Sryと呼ばれる遺伝子は、ほ乳類の性を決める(精巣を作る)ために必須です。ヒトを含めたすべてのほ乳類で、Sryはたったひとつのエキソンからなる遺伝子だと考えられていました。今回の私たちの研究は、マウスのSryがふたつのエキソンからなることを証明しました。Sryが発見されてから30年以上も経ちます。私たちの研究成果は、この間にすっと信じられてきた教科書の記載を書き換えるものとなりました。

Report

(3 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • Research Products

    (26 results)

All 2021 2020 2019 Other

All Int'l Joint Research (4 results) Journal Article (11 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 9 results,  Open Access: 8 results) Presentation (8 results) (of which Int'l Joint Research: 1 results,  Invited: 8 results) Remarks (3 results)

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

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Qeensland Universtity(オーストラリア)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] Th University of Blitish Columbia(カナダ)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] IGMM(フランス)

    • Related Report
      2019 Research-status Report
  • [Journal Article] Inhibition of histone methyltransferase G9a attenuates liver cancer initiation by sensitizing DNA-damaged hepatocytes to p53-induced apoptosis2021

    • Author(s)
      Takuma Nakatsuka, Keisuke Tateishi*, Hiroyuki Kato, Hiroaki Fujiwara, Keisuke Yamamoto, Yotaro Kudo, Hayato Nakagawa, Yasuo Tanaka, Hideaki Ijichi, Tsuneo Ikenoue, Takeaki Ishizawa, Kiyoshi Hasegawa, Makoto Tachibana, Yoichi Shinkai, Kazuhiko Koike
    • Journal Title

      Cell Death and Disease

      Volume: 12 Issue: 1 Pages: 99111-99111

    • DOI

      10.1038/s41419-020-03381-1

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] マウスの性決定遺伝子Sryにおける「隠れエキソン」の発見と、それがコードする真の性決定因子SRY-Tの発見2021

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

      実験医学

      Volume: 39 Pages: 571574-571574

    • Related Report
      2020 Annual Research Report
  • [Journal Article] G9a is involved in the regulation of cranial bone formation through activation of Runx2 function during development2020

    • Author(s)
      Ideno Hisashi、Nakashima Kazuhisa、Komatsu Koichiro、Araki Ryoko、Abe Masumi、Arai Yoshinori、Kimura Hiroshi、Shinkai Yoichi、Tachibana Makoto、Nifuji Akira
    • Journal Title

      Bone

      Volume: 137 Pages: 115332-115332

    • DOI

      10.1016/j.bone.2020.115332

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] H3K9 Demethylases JMJD1A and JMJD1B Control Prospermatogonia to Spermatogonia Transition in Mouse Germline2020

    • Author(s)
      Kuroki Shunsuke、Maeda Ryo、Yano Masashi、Kitano Satsuki、Miyachi Hitoshi、Fukuda Mikiko、Shinkai Yoichi、Tachibana Makoto
    • Journal Title

      Stem Cell Reports

      Volume: 15 Issue: 2 Pages: 424-438

    • DOI

      10.1016/j.stemcr.2020.06.013

    • NAID

      120007146093

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Deletion of Histone Methyltransferase G9a Suppresses Mutant Kras-driven Pancreatic Carcinogenesis Carcinogenesis2020

    • Author(s)
      Hiroyuki Kato, Keisuke Tateishi*, Hiroaki Fujiwara, Hideaki Ijichi, Keisuke Yamamoto, Takuma Nakatsuka, Miwako Kakiuchi, Makoto Sano, Yotaro Kudo, Yoku Hayakawa, Hayato Nakagawa, Yasuo Tanaka, Motoyuki Otsuka, Yoshihiro Hirata, Makoto Tachibana, Yoichi Shinkai, Kazuhiko Koike
    • Journal Title

      Cancer Genomics Proteomics

      Volume: 17 Issue: 6 Pages: 695705-695705

    • DOI

      10.21873/cgp.20224

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The mouse Sry locus harbors a cryptic exon that is essential for male sex determination2020

    • Author(s)
      Miyawaki Shingo、Kuroki Shunsuke、Maeda Ryo、Okashita Naoki、Koopman Peter、Tachibana Makoto
    • Journal Title

      Science

      Volume: 370 Issue: 6512 Pages: 121-124

    • DOI

      10.1126/science.abb6430

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Caspase-8, receptor-interacting protein kinase 1 (RIPK1), and RIPK3 regulate retinoic acid-induced cell differentiation and necroptosis.2019

    • Author(s)
      Someda M, Kuroki S, Miyachi H, Tachibana M, *Yonehara S.
    • Journal Title

      Cell Death Differ.

      Volume: - Issue: 5 Pages: 1539-1553

    • DOI

      10.1038/s41418-019-0434-2

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 遺伝子改変マウスの作成と技術進歩2019

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

      生産と技術

      Volume: 71 Pages: 15-20

    • Related Report
      2019 Research-status Report
  • [Journal Article] Role of epigenetic regulation in mammalian sex determination.2019

    • Author(s)
      Shingo Miyawaki, Makoto Tachibana
    • Journal Title

      Curr Top Dev Biol.

      Volume: 134 Pages: 195-221

    • DOI

      10.1016/bs.ctdb.2019.01.008

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Histone H3K9 Methyltransferase G9a in Oocytes Is Essential for Preimplantation Development but Dispensable for CG Methylation Protection.2019

    • Author(s)
      Yeung WKA, Brind’Amour J, Hatano Y, Yamagata K, Feil R, Matthew C. Lorincz MC, Tachibana M, Shinkai Y, Sasaki H*.
    • Journal Title

      Cell Rep.

      Volume: 27 Issue: 1 Pages: 282-293

    • DOI

      10.1016/j.celrep.2019.03.002

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] TET2 catalyzes active DNA demethylation of the Sry promoter and enhances its expression.2019

    • Author(s)
      Okashita N, Kuroki S, Maeda R, *Tachibana M.
    • Journal Title

      Sci Rep.

      Volume: 9 Issue: 1 Pages: 13462-13462

    • DOI

      10.1038/s41598-019-50058-7

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 真のオス化因子をコードするマウスSryの”隠れ”エキソンの発見2021

    • Author(s)
      立花 誠
    • Organizer
      日本エピジェネティクス研究会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] マウスSry遺伝子座には、これまで未同定でかつオス化に必須な役割を有する第2エキソンが存在する2020

    • Author(s)
      立花 誠、宮脇 慎吾、黒木 俊介、前田 亮、岡下 修己、Peter Koopman
    • Organizer
      日本分子生物学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 哺乳類の生殖における抑制的ヒストン修飾の役割2019

    • Author(s)
      立花誠
    • Organizer
      2019 遺伝研研究会 有性生殖に関わる染色体・クロマチン・核動態に関する研究会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] マウス性決定におけるエピゲノム制御の役割2019

    • Author(s)
      立花誠
    • Organizer
      日本DoHAD学会学術集会シンポジウム
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] H3K9のメチル化による生殖機能のエピジェネティック制御2019

    • Author(s)
      立花誠
    • Organizer
      日本遺伝学会第91回大会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Function of HP1 in H3K9 methylation dynamics2019

    • Author(s)
      立花誠
    • Organizer
      第42回日本分子生物学会年会シンポジウム
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] マウスY染色体のInverted repeat配列に存在する新規性決定領域の発見2019

    • Author(s)
      宮脇慎吾、黒木俊介、前田亮、岡下修己、立花誠
    • Organizer
      第42回日本分子生物学会年会ワークショップ
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Dynamic regulation of H3K9 methylation in germ cell development2019

    • Author(s)
      Makoto Tachibana
    • Organizer
      Gordon Research Conferences on Germinal Stem Cell Bilogy
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Remarks] 大阪大学大学院生命機能研究科立花研究室

    • URL

      https://www.fbs.osaka-u.ac.jp/labs/tachibana/

    • Related Report
      2020 Annual Research Report
  • [Remarks] 大阪大学生命機能研究科立花研HP

    • URL

      http://www.fbs.osaka-u.ac.jp/jpn/general/lab/072/

    • Related Report
      2019 Research-status Report
  • [Remarks] 新学術領域研究「性スペクトラム」

    • URL

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

    • Related Report
      2019 Research-status Report

URL: 

Published: 2019-07-04   Modified: 2022-01-27  

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