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Novel regulatory mechanisms of gene expression via Runx-dependent gene silencer

Research Project

Project/Area Number 18H02620
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 48040:Medical biochemistry-related
Research InstitutionKyushu University (2020-2021)
Institute of Physical and Chemical Research (2018-2019)

Principal Investigator

Kojo Satoshi  九州大学, 生体防御医学研究所, 准教授 (70360542)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2018: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Keywords転写因子RUNX / 胸腺細胞分化 / Cd4遺伝子 / サイレンサー / エンハンサーRNA / 遺伝子発現 / enhancer RNA / CD4 / RUNX / Silencer / Runx
Outline of Final Research Achievements

RUNX is a transcription factor that plays an important role in hematopoietic cell differentiation. One of the regulatory mechanisms of gene expression via RUNX is the repression of target gene expression by RUNX-dependent gene silencers, but the regulatory mechanism is largely unknown.
In this study, we identified gene regions in close proximity to the silencer in Cd4 gene locus. As a result, genomic proximity between the silencer and enhancer regions was observed in situations where silencer activity is high, suggesting that silencer-induced suppression of gene expression is induced by targeting the enhancer. The regulation of enhancer RNA expression was also suggested as a mechanism of gene repression by silencer.

Academic Significance and Societal Importance of the Research Achievements

遺伝子発現は生体を構成する細胞の機能や分化を司る極めて重要な生物学的プロセスである。また、免疫細胞は生体の防御を担う重要な細胞集団であり、その機能や分化機構を明らかにすることは重要な意味を持つ。本研究では、免疫細胞の一つT細胞の分化過程で生じる遺伝子発現について、新たな制御機構の存在を明らかにするものである。本機構は、免疫細胞分化のみならず様々な細胞で利用されている可能性もあり、生体の仕組みを理解するうえでの重要な発見であると考えられる。

Report

(4 results)
  • 2021 Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (17 results)

All 2022 2021 2020 2019 2018 Other

All Journal Article (4 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (12 results) (of which Int'l Joint Research: 1 results) Remarks (1 results)

  • [Journal Article] Runx-mediated regulation of CCL5 via antagonizing two enhancers influences immune cell function and anti-tumor immunity2020

    • Author(s)
      Seo Wooseok、Shimizu Kanako、Kojo Satoshi、Okeke Arinze、Kohwi-Shigematsu Terumi、Fujii Shin-ichiro、Taniuchi Ichiro
    • Journal Title

      Nature Communications

      Volume: 11 Issue: 1 Pages: 1-16

    • DOI

      10.1038/s41467-020-15375-w

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Constitutive CD8 expression drives innate CD8+ T-cell differentiation via induction of iNKT2 cells2020

    • Author(s)
      Kojo Satoshi、Ohno-Oishi Michiko、Wada Hisashi、Nieke Sebastian、Seo Wooseok、Muroi Sawako、Taniuchi Ichiro
    • Journal Title

      Life Science Alliance

      Volume: 3 Issue: 2 Pages: 1-13

    • DOI

      10.26508/lsa.202000642

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Runx/Cbfβ complexes protect group 2 innate lymphoid cells from exhausted-like hyporesponsiveness during allergic airway inflammation2019

    • Author(s)
      Miyamoto Chizuko、Kojo Satoshi、Yamashita Motoi、Moro Kazuyo、Lacaud Georges、Shiroguchi Katsuyuki、Taniuchi Ichiro、Ebihara Takashi
    • Journal Title

      Nature Communications

      Volume: 10 Issue: 1 Pages: 447-447

    • DOI

      10.1038/s41467-019-08365-0

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Runx-dependent and silencer-independent repression of a maturation enhancer in the Cd4 gene2018

    • Author(s)
      Kojo Satoshi、Yasmin Nighat、Muroi Sawako、Tenno Mari、Taniuchi Ichiro
    • Journal Title

      Nature Communications

      Volume: 9 Issue: 1 Pages: 3593-3593

    • DOI

      10.1038/s41467-018-05803-3

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Epigenomic and genetic approaches to identify Rorc enhancers indispensable for LTi cell development2022

    • Author(s)
      Satoshi Kojo, Takuma Fukui, Shinichiro Sawa
    • Organizer
      The 30th Hot Spring Harbor International Symposium
    • Related Report
      2020 Annual Research Report
  • [Presentation] A do novo missense mutation of Bcl11b gene causes an abnormal thymopoiesis2021

    • Author(s)
      Kazuki Okuyama, Motoi Yamashita, Kazuaki Matsumoto, Michiko Ohno-Oishi, Satoshi Kojo, Tomohiro Morio, Hideyuki Yoshida, Ichiro Taniuchi
    • Organizer
      50th Japanese Society for Immunology
    • Related Report
      2020 Annual Research Report
  • [Presentation] Phosphorylation of the last tyrosine residue regulates Runx1 function during T cell development2021

    • Author(s)
      Chihiro Ogawa, Satoshi Kojo, Kazuki Okuyama, Sawako Muroi, Ichiro Taniuchi
    • Organizer
      50th Japanese Society for Immunology
    • Related Report
      2020 Annual Research Report
  • [Presentation] Runx3 C末端アミノ酸残基による免疫細胞分化制御2019

    • Author(s)
      香城 諭, 海老原隆, 太野路子, 室井佐和子, 谷内一郎
    • Organizer
      第29回Kyoto T Cell Conference
    • Related Report
      2019 Annual Research Report
  • [Presentation] Bcl11b ミスセンス変異によるT細胞分化異常の発症機序2019

    • Author(s)
      奥山一生, 山下 基, 太野路子, 香城 諭, 谷内一郎
    • Organizer
      第29回Kyoto T Cell Conference
    • Related Report
      2019 Annual Research Report
  • [Presentation] Pathogenesis for T cell deficiency caused by a missense mutation of Bcl11b gene2019

    • Author(s)
      Kazuki Okuyama, Motoi Yamashita, Michiko Ohno, Satoshi Kojo, Hideyuki Yoshida, Ichiro Taniuchi
    • Organizer
      48th Japanese Society for Immunology
    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
  • [Presentation] Runx3 C末端アミノ酸残基による免疫細胞分化制御2019

    • Author(s)
      香城 諭, 海老原隆, 太野路子, 室井佐和子, 谷内一郎
    • Organizer
      第29回Kyoto T Cell Conference
    • Related Report
      2018 Annual Research Report
  • [Presentation] Bcl11b ミスセンス変異によるT細胞分化異常の発症機序2019

    • Author(s)
      奥山一生, 山下 基, 太野路子, 香城 諭, 谷内一郎
    • Organizer
      第29回Kyoto T Cell Conference
    • Related Report
      2018 Annual Research Report
  • [Presentation] Constitutive CD8 expression during thymocyte development drives differentiation of innate-like CD8+ T cell and NKT2 subset.2018

    • Author(s)
      Kojo S, Ohno-Oishi M, Muroi S, Taniuchi I
    • Organizer
      47th Japanese Society for Immunology
    • Related Report
      2018 Annual Research Report
  • [Presentation] Interactome study of Bcl11b during T cell development2018

    • Author(s)
      Okuyama K, Kojo S, Muroi S, Taniuchi I
    • Organizer
      47th Japanese Society for Immunology
    • Related Report
      2018 Annual Research Report
  • [Presentation] Constitutive CD8 expression drives innate-like CD8+ T cell differentiation via NKT2 induction.2018

    • Author(s)
      Kojo S, Ohno-Oishi M, Wada H, Nieke S, Muroi S, Taniuchi I
    • Organizer
      The 3rd International Conference on Innate Lymphoid Cells.
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] An enhancer RNA is a crucial target of Runx-dependent silencer for Cd4 gene repression2018

    • Author(s)
      香城 諭, 室井佐和子, 谷内一郎
    • Organizer
      第28回 Kyoto T Cell Conference
    • Related Report
      2018 Annual Research Report
  • [Remarks] 新たなT細胞分化制御機構を発見 -Cd4サイレンサー非依存的なCd4遺伝子発現制御-

    • URL

      https://www.riken.jp/press/2018/20180905_1/index.html

    • Related Report
      2018 Annual Research Report

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Published: 2018-04-23   Modified: 2023-01-30  

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