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Elucidation of transcription-coupled facultative heterochromatin dynamics

Research Project

Project/Area Number 16K07249
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Molecular biology
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

Ohhata Tatsuya  浜松医科大学, 医学部, 助教 (80616459)

Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsエピジェネティクス / X染色体不活性化 / ノンコーディングRNA / アンチセンスRNA / cisNATs / Tsix / ヘテロクロマチン / クロマチン / ダイナミクス / 非コードRNA / lncRNA
Outline of Final Research Achievements

The fine-scale dynamics of epigenetic switching from euchromatin (EC) to facultative heterochromatin (fHC) has remained largely unclear. Here, we focused on Xist and its silencing initiator Tsix as a paradigm of transcription-mediated epigenetic switching. Studying the dynamics revealed that the conversion proceeds in a stepwise manner: initially, transient activation accompanied by active epigenetic alterations and opened chromatin structure is observed. In the second step, gene silencing is initiated that is initiator-dependent and reversible and accompanied by simultaneous changes of multiple histone modifications. At the last step, silencing becomes initiator-independent and irreversible, correlated with DNA methylation introduction. This choreography provides fundamental information to understand the mechanism of gene regulation via epigenetic machinery.

Academic Significance and Societal Importance of the Research Achievements

本研究は、Tsix RNA によるエピジェネティック修飾および構造変化の関係性及び階層性を明らかにした。この成果は、アンチセンス転写による制御機構の理解に留まらず、エピジェネティクスを介した遺伝子発現制御機構といった、さらに一般的な基礎研究領域にも貢献する。
発生段階や細胞分化に応じてヘテロクロマチン化する領域は条件的ヘテロクロマチンとよばれており、この時間空間特異的な発現調節機構の理解は、再生医療や老化、その破綻によるがんを含む各種疾患への関与など、その応用面でも注目されている。本研究成果により明らかとなった条件的へテロクロマチン形成機構の理解は、各種疾患への応用へも期待される。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (18 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (3 results) Presentation (14 results) (of which Int'l Joint Research: 3 results) Book (1 results)

  • [Int'l Joint Research] ETH(スイス)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] ETH(スイス)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] ETH(スイス)

    • Related Report
      2016 Research-status Report
  • [Presentation] 単一遺伝子座における条件的ヘテロクロマチンダイナミクス2019

    • Author(s)
      Tatsuya Ohhata, Kazuki Yamasawa, Asuka Miura-kamio, Saori Takahashi, Ichiro Hiratani, Hisato Kobayashi, Hiroshi Kimura, Anton Wutz, Masatoshi Kitagawa
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Dynamics from euchromatin to facultative heterochromatin in local gene silencing2019

    • Author(s)
      Tatsuya Ohhata
    • Organizer
      第6回北陸エピジェネティクス研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] A snapshot of facultative heterochromatin dynamics revealed by antisense long non-coding RNA Tsix2018

    • Author(s)
      大畑 樹也
    • Organizer
      第6回 X染色体研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] A snapshot of facultative heterochromatin dynamics revealed by antisense long non-coding RNA Tsix2018

    • Author(s)
      大畑 樹也
    • Organizer
      第41回 日本分子生物学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Dynamics of repressive chromatin conformation at the Xist promoter revealed by Tsix-inducible system2017

    • Author(s)
      Tatsuya Ohhata
    • Organizer
      第22回浜松医科学シンポジウム
    • Place of Presentation
      浜松市、静岡県
    • Year and Date
      2017-03-10
    • Related Report
      2016 Research-status Report
  • [Presentation] アンチセンス非コードRNA Tsix による条件的ヘテロクロマチン形成機構の動的解析2017

    • Author(s)
      Tatsuya Ohhata, Hiroshi Kimura, Kazuki Yamazawa, Anton Wutz, Masatoshi Kitagawa
    • Organizer
      第11回 日本エピジェネティクス研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] Dynamics of faclutative heterochromatin formation at the Xist promoter evoked by antisense long non-coding RNA Tsix2017

    • Author(s)
      Tatsuya Ohhata, Hiroshi Kimura, Kazuki Yamazawa, Anton Wutz, Masatoshi Kitagawa
    • Organizer
      The 43rd Naito Conference on "Noncoding RNA: Biology, Chemistry, & Diseases"
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] A snapshot of facultative heterochromatin dynamics revealed by antisense long non-coding RNA Tsix2017

    • Author(s)
      Tatsuya Ohhata, Hiroshi Kimura, Kazuki Yamazawa, Asuka Miura-Kamio, Hisato Kobayashi, Anton Wutz, Masatoshi Kitagawa
    • Organizer
      Gordon Research Conference, Epigenetics
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] A snapshot of facultative heterochromatin dynamics revealed by antisense long non-coding RNA Tsix2017

    • Author(s)
      大畑 樹也
    • Organizer
      第5回 X染色体研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] A snapshot of facultative heterochromatin dynamics revealed by antisense long non-coding RNA Tsix2017

    • Author(s)
      大畑 樹也
    • Organizer
      第4回 北陸エピジェネティクス研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] アンチセンスRNA TsixはH3K36me3をXistプロモーターに導入しXistの発現を抑制する2016

    • Author(s)
      大畑樹也、松本美香、Martin Leeb、柴田進和、北川恭子、丹伊田浩行、酒井聡、Anton Wutz、北川雅敏
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      横浜市、神奈川県
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
  • [Presentation] Investigating the molecular mechanisms of Tsix antisense RNA involved in the Regulation of X-chromosome inactivation2016

    • Author(s)
      Tatsuya Ohhata
    • Organizer
      第3回北陸エピジェネティクス研究会
    • Place of Presentation
      福井市、福井県
    • Year and Date
      2016-11-21
    • Related Report
      2016 Research-status Report
  • [Presentation] Dynamics of repressive chromatin conformation at the Xist promoter revealed by Tsix-inducible system2016

    • Author(s)
      Tatsuya Ohhata
    • Organizer
      X chromosome inactivation -A tribute to Mary Lyon-
    • Place of Presentation
      Royal society, London, UK
    • Year and Date
      2016-10-03
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 条件的ヘテロクロマチン形成機構の解明を目指して2016

    • Author(s)
      大畑樹也
    • Organizer
      第1回浜松医科大学学内研究交流会
    • Place of Presentation
      舘山寺温泉、浜松市
    • Year and Date
      2016-07-17
    • Related Report
      2016 Research-status Report
  • [Book] lncRNAと疾患, ノンコーディングRNA -RNA分子の全体像を俯瞰する-2016

    • Author(s)
      大畑樹也
    • Total Pages
      12
    • Publisher
      化学同人
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2021-02-19  

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