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Analysis of hematopoietic regulation mechanisms by a novel repressor for RUNX1

Research Project

Project/Area Number 17K09936
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Hematology
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

YOSHIDA TATSUSHI  京都府立医科大学, 医学(系)研究科(研究院), 講師 (80315936)

Co-Investigator(Kenkyū-buntansha) 奥田 司  京都府立医科大学, 医学(系)研究科(研究院), 教授 (30291587)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsRUNX1 / 白血病 / 造血 / 転写因子 / 転写制御 / RIUNX1
Outline of Final Research Achievements

RUNX1 gene is frequently point mutated or chromosomal translocated in acute leukemia and myelodisplasia. RUNX1 is essential for definitive hematopoiesis in fatal liver and plays a role in hematopoietic development in adult. RUNX1 acts as a transcription factor and regulates gene expression related to hematopoiesis, however regulation of RUNX1 itself has not been elucidated fully. Thus, we identified CRP1, a novel binding factor of RUNX1 and found that it repressed transcriptional regulation by RUNX1. In this research project, we analyzed the mechanism in which CRP1 affected to RUNX1 function and the effect of CRP1 on hematopoiesis regulated by RUNX1 in gene-modified mice. In addition we performed an establishment of a screening system to search compounds which can block the interaction between RUNX1 and CRP1.

Academic Significance and Societal Importance of the Research Achievements

RUNX1は白血病発症や造血分化異常と関連する因子であるが、RUNX1の機能を調節する効果的な手法は今まで報告されていなかった。本研究では、新たなRUNX1結合因子を発見し、そしてその因子がRUNX1機能に及ぼす影響を解析した。この因子とRUNX1との相互作用を標的とすることによって、RUNX1の機能不全を回復することができ、将来的には白血病や造血異常の改善に結び付くことが示唆された。したがって、本研究成果は十分な学術的意義および社会的意義を有していると考えられた。

Report

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

    (13 results)

All 2019 2018 2017

All Journal Article (1 results) (of which Open Access: 1 results) Presentation (12 results)

  • [Journal Article] 細胞死とがん2019

    • Author(s)
      吉田達士,山崎健太,奥田司
    • Journal Title

      Journal of Kyoto Prefectural University of Medicine

      Volume: 128 Issue: 2 Pages: 81-99

    • DOI

      10.32206/jkpum.128.02.081

    • ISSN
      0023-6012
    • Year and Date
      2019-02-25
    • Related Report
      2018 Research-status Report
    • Open Access
  • [Presentation] 転写因子RUNX1/AML1の新規候補標的遺伝子群の探索2019

    • Author(s)
      忠垣憲次郎、山崎健太、近藤則子、桒原康通、吉田達士、奥田司
    • Organizer
      第92回日本生化学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Analysis of a novel transcriptional target gene of RUNX1.2019

    • Author(s)
      Tatsushi YOSHIDA, Kenjiro TADAGAKI, Yasumichi KUWAHARA, Toshiyuki SAKAI, and Tsukasa OKUDA
    • Organizer
      第78回 日本癌学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Identification of a novel RUNX1 target by public data re-analysis that is suppressed by RUNX1-ETO2019

    • Author(s)
      Akifumi Matsumoto, Tatsushi Yoshida, Takahiro Shima, Kenta Yamasaki, Kenjiro Tadagaki, Noriko Kondo, Yasumichi Kuwahara, Donger Zhang, Tsukasa Okuda
    • Organizer
      第81回日本血液学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 造血関連転写因子 RUNX1による制御遺伝子の探索2019

    • Author(s)
      山崎 健太、忠垣 憲次郎、近藤 則子、桑原 康通、吉田 達士、奥田 司
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] A novel transcriptional target of RUNX1.2018

    • Author(s)
      Tatsushi YOSHIDA, Kenta YAMASAKI, Kenjiro TADAGAKI, Yasumichi KUWAHARA, Noriko KONDO, Akifumi MATSUMOTO, Toshiyuki SAKAI, and Tsukasa OKUDA.
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Functional interaction between SWI/SNF complex and a hematopoietic transcription factor in malignant rhabdoid tumor.2018

    • Author(s)
      Yasumichi KUWAHARA, Tatsushi YOSHIDA, Kenjirou TADAGAKI and Tsukasa OKUDA.
    • Organizer
      第77回 日本癌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Analysis of a novel candidate target gene of the hematopoietic transcription factor RUNX1 (AML1).2018

    • Author(s)
      Kenjiro Tadagaki, Kenta Yamasaki, Noriko Kondo, Yasumichi Kuwahara, Tatsushi Yoshida, Tsukasa Okuda.
    • Organizer
      第80回日本血液学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 造血関連転写因子RUNX1(AML1)の新規転写標的候補遺伝子の探索2018

    • Author(s)
      忠垣憲次郎、山崎健太、近藤則子、桒原康通、吉田達士、奥田司
    • Organizer
      第41回日本分子生物学会
    • Related Report
      2018 Research-status Report
  • [Presentation] RUNX1/AML1転写因子の新規候補標的遺伝子の解析2017

    • Author(s)
      忠垣憲次郎、山崎健太、桒原康道、吉田達士、奥田司
    • Organizer
      第64回日本生化学会近畿支部例会
    • Related Report
      2017 Research-status Report
  • [Presentation] An array-based approach for novel RUNX1(AML1)-target genes.2017

    • Author(s)
      Kenjiro Tadagaki, Yasumichi Kuwahara, Tatsushi Yoshida, Tsukasa Okuda.
    • Organizer
      第76回日本癌学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Candidate target genes of hematopoietic transcription factor RUNX1 (AML1).2017

    • Author(s)
      Kenjiro Tadagaki, Kenta Yamasaki, Yasumichi Kuwahara, Tatsushi Yoshida, Tsukasa Okuda.
    • Organizer
      第79回日本血液学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Mechanism of recruitment of SWI/SNF complex via interaction between SNF5 and transcription factor.2017

    • Author(s)
      Yasumichi Kuwahara, Kenta Yamasaki, Kenjiro Tadagaki, Tatsushi Yoshida, Tsukasa Okuda
    • Organizer
      2017年度生命科学系学会合同年次大会(第40回日本分子生物学会年会/第90回日本生化学会大会)
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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