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Establishment and dynamics of the centromere chromatin, which ensure the faithful genome inheritance

Research Project

Project/Area Number 20H03236
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

Hori Tetsuya  大阪大学, 大学院生命機能研究科, 准教授 (70550078)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2022: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2021: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2020: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Keywordsセントロメア / クロマチン / エピジェネティックス / 細胞周期 / 染色体 / ゲノム
Outline of Research at the Start

本研究では、(1)細胞周期の進行に伴うセントロメアタンパク質のクロマチンへの結合量の変動の解析、(2)細胞周期を同調した細胞を用いた、ATAC-seq法およびHi-CO法によるセントロメアクロマチンの3次元配置の解析、(3)M期およびG1期のセントロメアクロマチンの構造形成に必須な因子の同定、を行い、細胞内におけるセントロメアクロマチンの構造と構築メカニズムをヌクレオソーム単位で解析する。そして、これまで未解明であった細胞周期に依存したクロマチン構造の変化を基盤としたセントロメア機能を制御する仕組みと、クロマチン構造変換の生物学的な意義を明らかにする。

Outline of Final Research Achievements

We found a critical CENP-A residue essential for faithful chromosome segregation. Moreover, we demonstrated that this residue was required for the proper complex formation with the CENP-A specific chaperon HJURP. Based on the structural analyses, we identified several contact sites of KNL2 to make a complex with CENP-A nucleosome, which was essential for the KNL2 localization and function. Furthermore, the artificial ectopic tethering assays indicated the additional CENP-A loading pathway depending on the CENP-C interaction with HJURP. These findings may provide insight into developing an anti-cancer drug utilizing centromeric chromatin modulation.

Academic Significance and Societal Importance of the Research Achievements

遺伝情報の継承に重要な、細胞核内のセントロメアのクロマチンの形成の仕組みと、その安定維持を保証するメカニズムの一端を明らかにした。これら成果は、細胞の遺伝情報の伝播の仕組みを解明する鍵となる知見として期待される。さらに将来的には、これら成果を活用した抗がん剤などの新規薬剤開発研究への応用が期待される。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (24 results)

All 2023 2022 2021 2020 Other

All Int'l Joint Research (5 results) Journal Article (5 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (9 results) (of which Invited: 2 results) Remarks (5 results)

  • [Int'l Joint Research] エジンバラ大学(英国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] エジンバラ大学(英国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] ハーバード大学(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] エジンバラ大学(英国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] ロックフェラー大学(米国)

    • Related Report
      2020 Annual Research Report
  • [Journal Article] The cryo‐EM structure of the CENP‐A nucleosome in complex with ggKNL22023

    • Author(s)
      Jiang Honghui、Ariyoshi Mariko、Hori Tetsuya、Watanabe Reito、Makino Fumiaki、Namba Keiichi、Fukagawa Tatsuo
    • Journal Title

      The EMBO Journal

      Volume: 42 Issue: 6

    • DOI

      10.15252/embj.2022111965

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Bridgin connects the outer kinetochore to centromeric chromatin.2021

    • Author(s)
      Sridhar S, Hori T, Nakagawa R, Fukagawa T, Sanyal K.
    • Journal Title

      Nat Commun.

      Volume: 12 Issue: 1 Pages: 146-146

    • DOI

      10.1038/s41467-020-20161-9

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] H3K9me3 maintenance on a human artificial chromosome is required for segregation but not centromere epigenetic memory.2020

    • Author(s)
      Martins NMC, Cisneros-Soberanis F, Pesenti E, Kochanova NY, Shang WH, Hori T, Nagase T, Kimura H, Larionov V, Masumoto H, Fukagawa T, Earnshaw WC.
    • Journal Title

      J Cell Sci.

      Volume: 133 Issue: 14

    • DOI

      10.1242/jcs.242610

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Essentiality of CENP-A Depends on Its Binding Mode to HJURP.2020

    • Author(s)
      Tetsuya Hori , JingHui Cao , Kohei Nishimura , Mariko Ariyoshi , Yasuhiro Arimura , Hitoshi Kurumizaka , Tatsuo Fukagawa
    • Journal Title

      Cell reports

      Volume: 33 Issue: 7 Pages: 108388-108388

    • DOI

      10.1016/j.celrep.2020.108388

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 染色体分配に必須なセントロメアのクロマチン構造2020

    • Author(s)
      堀哲也、深川竜郎
    • Journal Title

      細胞

      Volume: 52 Pages: 342-347

    • Related Report
      2020 Annual Research Report
  • [Presentation] 動原体タンパク質に依存したセントロメアの位置情報の書き込みメカニズム2022

    • Author(s)
      堀 哲也, 曹静暉, 深川竜郎
    • Organizer
      日本遺伝学会第94回大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] CCAN-dependent CENP-A assembly mechanism in vertebrate cells.2022

    • Author(s)
      Hori Tetsuya, Cao Jinghui, Fukagawa Tatsuo
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Analysis for the CENP-I dependent CENP-A incorporation into centromeres2022

    • Author(s)
      Cao Jinghui, Hori Tetsuya, Fukagawa Tatsuo
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] セントロメアのクロマチン構造とエピジェネティックス2021

    • Author(s)
      堀哲也
    • Organizer
      日本遺伝学会第93回大会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] CENP-Iに依存するCENP-A導入経路の解析2021

    • Author(s)
      曹静暉, 堀哲也, 深川竜郎
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Evolutional diversity of CENP-A essential motif and its binding mode to HJURP2020

    • Author(s)
      Tetsuya Hori、Jinghui Cao、Yasuhiro Arimura、Kohei Nishimura、Mariko Ariyoshi、Atsushi Toyoda、Sadahiko Misu、Kazuho Ikeo、Hitoshi Kurumizaka、Tatsuo Fukagawa
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Biochemical analysis of interaction between CENP-A/H4 and HJURP2020

    • Author(s)
      Jinghui Cao、Yasuhiro Arimura、Mariko Ariyoshi、Hitoshi Kurumizaka、Tetsuya Hori、Tatsuo Fukagawa
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] セントロメアのエピジェネティックスと進化2020

    • Author(s)
      堀哲也
    • Organizer
      日本遺伝学会第92回大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] H2A.Zヒストンバリアントアイソフォーム間における酸化ストレス応答遺伝子EGR1転写制御機構の差異の解析2020

    • Author(s)
      荻原望、高橋大輔、堀哲也、深川竜郎、原田昌彦
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
  • [Remarks] 深川研究室・研究成果、多数の国内外メディアにて報道

    • URL

      https://www.fbs.osaka-u.ac.jp/ja/news/detail/689

    • Related Report
      2022 Annual Research Report
  • [Remarks] 深川研究室・研究成果からの画像、EMBOジャーナル3月号の表紙に選出

    • URL

      https://www.fbs.osaka-u.ac.jp/ja/news/detail/702

    • Related Report
      2022 Annual Research Report
  • [Remarks] 細胞分裂に働く因子の新知見。鍵を握るヒト特有のアミノ酸

    • URL

      https://www.fbs.osaka-u.ac.jp/ja/research_results/papers/detail/1010

    • Related Report
      2020 Annual Research Report
  • [Remarks] 細胞分裂に働く因子の新知見。鍵を握るヒト特有のアミノ酸

    • URL

      https://resou.osaka-u.ac.jp/ja/research/2020/20201118_1

    • Related Report
      2020 Annual Research Report
  • [Remarks] 世界初!!クリプトコッカス独自の細胞分裂機構を解明

    • URL

      https://www.fbs.osaka-u.ac.jp/ja/research_results/papers/detail/1013

    • Related Report
      2020 Annual Research Report

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Published: 2020-04-28   Modified: 2024-01-30  

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