Evolution of mammalian sex-determining system by insertion of transposons
| Project/Area Number |
19K22388
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
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| Research Institution | Osaka University |
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Principal Investigator |
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| Project Period (FY) |
2019-06-28 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| 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)
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| Keywords | 性決定遺伝子 / トランスポゾン / 性決定 / Y染色体 |
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| 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。
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| 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.
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| 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。
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Report
(3 results)
Research Products
(26 results)
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[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
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Journal Title
Cell Death and Disease
Volume: 12
Issue: 1
Pages: 99111-99111
DOI
Related Report
Peer Reviewed / Open Access
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[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
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Journal Title
Cancer Genomics Proteomics
Volume: 17
Issue: 6
Pages: 695705-695705
DOI
Related Report
Peer Reviewed / Open Access
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