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Roles of phase separation in genome biology and cancer biology

Research Project

Project/Area Number 19K24694
Research Category

Fund for the Promotion of Joint International Research (Home-Returning Researcher Development Research)

Allocation TypeMulti-year Fund
Review Section Biological Sciences
Research InstitutionNagoya University

Principal Investigator

Suzuki Hiroshi  名古屋大学, 医学系研究科, 教授 (00587793)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥56,030,000 (Direct Cost: ¥43,100,000、Indirect Cost: ¥12,930,000)
Keywordsゲノム / RNA / 相分離 / エンハンサー / がん
Outline of Final Research Achievements

This study aimed to investigate the roles of (liquid-liquid) phase separation (LLPS) in regulation of regulatory elements in the genome and, particularly, super-enhancers toward better understanding of alteration in gene regulation and biomolecular condensates in cancers. By focusing on the RNA exosome, which degrades many unstable RNAs in the nucleus, we have identified the regulatory roles of the RNA exosome in regulation of super-enhancers and transcriptional condensates. We have also studied the roles of intrinsically disordered regions (IDRs), major drivers of LLPS, and extrachromosomal circular DNAs (eccDNAs) in cancer cells. Furthermore, by expanding the expertise in computational modeling in previous studies, additional collaboration project has successfully developed new CRISPR-based genome editing strategy, called “safeguard sgRNA” strategy, which improves the safety and applicability of genome editing.

Academic Significance and Societal Importance of the Research Achievements

近年の研究により、転写制御やゲノム制御において、(液液)相分離と呼ばれる現象が重要な役割を果たす可能性が示唆されている。一方で、核内で転写因子や転写調節因子からなる相分離凝集体(転写凝集体)がどのように形成され、ゲノムと相互作用し、遺伝子の発現を制御するのかという基本的な分子機構はほとんど解明されていない。本研究では、非コード領域からの転写・RNA産生がどのように転写凝集体を制御しているのかという点に注目し、転写凝集体の基本的分子メカニズムに関する重要な知見を得ることができた。さらに、天然変性領域や染色体外環状DNAに関する研究は新しいがん研究の展開やがん治療の開発につながることが期待される。

Report

(2 results)
  • 2022 Final Research Report ( PDF )
  • 2020 Research-status Report
  • Research Products

    (13 results)

All 2021 2020 Other

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

  • [Int'l Joint Research] マサチューセッツ工科大学(米国)

    • Related Report
      2020 Research-status Report
  • [Journal Article] 「柿の種」留学の意味 : 早石修記念海外留学助成による留学体験記2021

    • Author(s)
      鈴木 洋
    • Journal Title

      生化学

      Volume: 92 Issue: 6 Pages: 857-857

    • Related Report
      2020 Research-status Report
  • [Journal Article] 転写凝集体とゲノム高次構造2021

    • Author(s)
      鈴木 洋
    • Journal Title

      実験医学増刊

      Volume: 39 Issue: 10

    • Description
      印刷中
    • Related Report
      2020 Research-status Report
  • [Journal Article] Combined Cohesin-Runx1 Deficiency Synergistically Perturbs Chromatin Looping and Causes Myelodysplastic Syndromes2020

    • Author(s)
      Ochi Y, Ogawa Seishi., et al.
    • Journal Title

      Cancer Discov

      Volume: - Issue: 6 Pages: 836-853

    • DOI

      10.1158/2159-8290.cd-19-0982

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Chd4 choreographs self-antigen expression for central immune tolerance2020

    • Author(s)
      Yoshihiko Tomofuji, Hiroyuki Takaba, Hiroshi I Suzuki, Rayene Benlaribi, Cristian David Pena Martinez, Yoshihiro Abe, Yasuyuki Morishita, Tadashi Okamura, Akashi Taguchi, Tatsuhiko Kodama, Hiroshi Takayanagi
    • Journal Title

      Nature Immunology

      Volume: 8 Issue: 8 Pages: 892-901

    • DOI

      10.1038/s41590-020-0717-2

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] FOXL1 Regulates Lung Fibroblast Function via Multiple Mechanisms.2020

    • Author(s)
      Miyashita N, Horie M, Suzuki HI, Saito M, Mikami Y, Okuda K, Boucher RC, Suzukawa M, Hebisawa A, Saito A, Nagase T.
    • Journal Title

      American Journal of Respiratory Cell and Molecular Biology

      Volume: 63 Issue: 6 Pages: 831-842

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] MCPIP1 reduces HBV-RNA by targeting its epsilon structure2020

    • Author(s)
      Li Yingfang、Que Lusheng、Fukano Kento、Koura Miki、Kitamura Kouichi、Zheng Xin、Kato Takanobu、Aly Hussein Hassan、Watashi Koichi、Tsukuda Senko、Aizaki Hideki、Watanabe Noriyuki、Sato Yuko、Suzuki Tadaki、Suzuki Hiroshi I.、Hosomichi Kazuyoshi、Kurachi Makoto、Wakae Kousho、Muramatsu Masamichi
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 20763-20763

    • DOI

      10.1038/s41598-020-77166-z

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ヒト疾患におけるマイクロRNAの機能獲得型変異の発見2020

    • Author(s)
      鈴木 洋
    • Journal Title

      実験医学

      Volume: 37 Issue: 14 Pages: 2322-2325

    • Related Report
      2020 Research-status Report
  • [Journal Article] 相分離とスーパーエンハンサーによる遺伝子制御2020

    • Author(s)
      鈴木 洋
    • Journal Title

      現代科学増刊46 相分離生物学の全貌

      Volume: 46 Pages: 152-156

    • Related Report
      2020 Research-status Report
  • [Presentation] データ駆動型サイエンスによるゲノムRNAネットワークの理解2021

    • Author(s)
      鈴木 洋
    • Organizer
      Onlineサイエンス倶楽部
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Mysteries of gene regulation ~beyond super-enhancers~2021

    • Author(s)
      Hiroshi I. Suzuki
    • Organizer
      東京大学免疫学セミナー
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 遺伝子制御と相分離2021

    • Author(s)
      鈴木 洋
    • Organizer
      名古屋大学相分離生物学セミナー
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Understanding the nexus of genome complexity and transcription dynamics2020

    • Author(s)
      Hiroshi I. Suzuki
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Research-status Report
    • Invited

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Published: 2020-03-25   Modified: 2024-01-30  

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