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Study of H3K9me reader of mammalian sex-determining gene Sry

Research Project

Project/Area Number 18H02419
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 43050:Genome biology-related
Research InstitutionOsaka University

Principal Investigator

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

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2019: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2018: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Keywords性分化 / Sryエピゲノム / エピゲノム / クロモドメイン / 性決定 / H3K9メチル化 / クロモドメインタンパク質 / エピゲノム制御
Outline of Final Research Achievements

Epigenetic regulation by histone modification is achieved by the cooperative action of writer, eraser and reader of histones. Cdyl family molecules and HP1 family molecules are chromodomain-containing proteins that can recognize methylated H3K9. In this study, we analyzed the functions of Cdyl family molecules and HP1 family molecules in mouse sex differentiation, to clarify their role as the reader molecule of methylated H3K9 at the Sry locus. We established Cdyl, Cdyl2, and HP1α-deficient mice and then observbed their phenotypes. We did not find abnormalities n sexual differentiation in these mice. However, on the contrary to the initial expectation, genetic analysis under the Jmjd1a-deficient background revealed that Cdyl and Cdyl2 positively regulate male development.

Academic Significance and Societal Importance of the Research Achievements

ほ乳類の性決定遺伝子の発現にエピゲノムが重要であることを私たちは過去に報告しました。この成果を踏まえ本研究では、マウスの性決定遺伝子の発現を抑制すると想定される(すなわちメス化を促すと想定される)エピゲノム読み取り分子、Cdylの機能を解析しました。その結果、予想に反して本分子はオス化を促す機能があることが分かりました。今後はCdylと人の性分化疾患の発症とのが関わりが注目されます。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (38 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (4 results) Journal Article (18 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 13 results,  Open Access: 12 results) Presentation (12 results) (of which Int'l Joint Research: 2 results,  Invited: 12 results) Remarks (4 results)

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

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

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] The University of Blitish Columbia(カナダ)

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

    • Related Report
      2019 Annual Research 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 Annual Research 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 Annual Research 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 Annual Research 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 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] TET2 catalyzes active DNA demethylation of the Sry promoter and enhances its expression2019

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

      Sci Rep.

      Volume: 9 Pages: 13462-13462

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] G9a-dependent histone methylation can be induced in G1 phase of cell cycle.2019

    • Author(s)
      Fukuda M, Sakaue-Sawano A, Shimura C, Tachibana M, Miyawaki A, *Shinkai Y.
    • Journal Title

      Sci Rep.

      Volume: 9 Pages: 956-956

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 性とは何か:雌雄間の多様な性2019

    • Author(s)
      立花誠
    • Journal Title

      現代化学

      Volume: 574 Pages: 40-43

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Combined loss of JMJD1A and JMJD1B reveals critical roles for H3K9 demethylation in the maintenance of embryonic stem cells and early embryogenesis.2018

    • Author(s)
      Kuroki, S., Nakai, Y., Maeda, R., Okashita, N., Akiyoshi, M., Yamaguchi, Y., Kitano, S., Miyachi, H., Nakato, R., Ichiyanagi, K., Shirahige, K., Kimura, H., Shinkai, Y., and Tachibana, M.
    • Journal Title

      Stem Cell Rep.

      Volume: 10 Issue: 4 Pages: 1340-1354

    • DOI

      10.1016/j.stemcr.2018.02.002

    • NAID

      120006463740

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] FGF2 Has Distinct Molecular Functions from GDNF in the Mouse Germline Niche2018

    • Author(s)
      Masaki Kaito、Sakai Mizuki、Kuroki Shunsuke、Jo Jun-Ichiro、Hoshina Kazuo、Fujimori Yuki、Oka Kenji、Amano Toshiyasu、Yamanaka Takahiro、Tachibana Makoto、Tabata Yasuhiko、Shiozawa Tanri、Ishizuka Osamu、Hochi Shinichi、Takashima Seiji
    • Journal Title

      Stem Cell Reports

      Volume: 10 Issue: 6 Pages: 1-11

    • DOI

      10.1016/j.stemcr.2018.03.016

    • NAID

      120007037475

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] DNMTs and SETDB1 function as co-repressors in MAX-mediated repression of germ cell-related genes in mouse embryonic stem cells2018

    • Author(s)
      Tatsumi Daiki、Hayashi Yohei、Endo Mai、Kobayashi Hisato、Yoshioka Takumi、Kiso Kohei、Kanno Shinichiro、Nakai Yuji、Maeda Ikuma、Mochizuki Kentaro、Tachibana Makoto、Koseki Haruhiko、Okuda Akihiko、Yasui Akira、Kono Tomohiro、Matsui Yasuhisa
    • Journal Title

      PLOS ONE

      Volume: 13 Issue: 11 Pages: e0205969-e0205969

    • DOI

      10.1371/journal.pone.0205969

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] タンパク質・核酸の分子修飾 -メチル化2018

    • Author(s)
      前田亮、*立花誠
    • Journal Title

      生体の科学[増大特集]

      Volume: 69 Pages: 404-405

    • Related Report
      2018 Annual Research Report
  • [Journal Article] タンパク質・核酸の分子修飾 -脱メチル化2018

    • Author(s)
      岡下修己、*立花誠
    • Journal Title

      生体の科学[増大特集]

      Volume: 69 Pages: 406-407

    • Related Report
      2018 Annual Research Report
  • [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 Annual Research 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 Annual Research 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 Annual Research 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 Annual Research 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 Annual Research 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, Hong Kong, China
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] H3K9 methylation dynamics for mammalian reproduction2018

    • Author(s)
      Makoto Tachibana
    • Organizer
      The 8th International symposium on vertebrate sex determination
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ほ乳類の性決定におけるエピゲノム制御の役割2018

    • Author(s)
      立花誠
    • Organizer
      第91回日本内分泌学会総会シンポジウム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 哺乳類の性決定におけるエピゲノム制御の役割2018

    • Author(s)
      立花誠
    • Organizer
      再生学異分野融合研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 哺乳類性決定のエピジェネティックな制御機構2018

    • Author(s)
      立花誠
    • Organizer
      第37回動物生殖工学研究会
    • Related Report
      2018 Annual Research Report
    • 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] 大阪大学大学院生命機能研究科立花研究室

    • URL

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

    • Related Report
      2019 Annual Research Report
  • [Remarks] 新学術研究領域「性スペクトラム」

    • URL

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

    • Related Report
      2019 Annual Research Report
  • [Remarks] 性スペクトラム-連続する表現型としての雌雄-

    • URL

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

    • Related Report
      2018 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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