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Elucidation of cell differentiation by hematopoietic transcription factor RUNX1 and translation to a novel molecular target strategy

Research Project

Project/Area Number 19K08845
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 54010:Hematology and medical oncology-related
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

TADAGAKI Kenjiro  京都府立医科大学, 医学(系)研究科(研究院), 助教 (30416268)

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) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords造血幹細胞 / 転写因子 / RUNX1 / 遺伝子発現制御 / プロモーター / Runx1 / 遺伝子発現
Outline of Research at the Start

造血幹細胞は多分化能と自己複製能を併せ持つ高い増殖能力を有する細胞であるが、その初期発生・自己複製・分化や血液細胞の産生・維持の分子機構には不明の点が数多く残されている。本研究は、造血幹細胞の発生・分化において必須な転写因子であり、白血病発症における遺伝子変異の標的となるRUNX1(AML1)のプロモーター解析とその遺伝子発現制御に関わる因子を新規に同定することで、造血幹細胞発生制御、血小板産生、そしてT細胞分化に関わる分子機構の解明を目指すものである。本研究を通じて、RUNX1を介した造血発生・分化制御の分子メカニズムの理解が大きく進むものと期待できる。

Outline of Final Research Achievements

RUNX1 gene acts as a hematopoietic transcription factor and is a frequent target of leukemia-related gene aberrations, however regulation of RUNX1 expression has not been elucidated fully. In this project, we focused on the identification of the novel transcriptional factors for RUNX1 and selected six candidate transcriptional factors which regulated RUNX1 promoter activity detected by luciferase reporter assay. We found that the message level of RUNX1 gene was regulated depending on the five transcriptional factors of the six status in the cell-level experiments. In addition, ChIP assay showed that the four transcriptional factors of six bound to the RUNX1 promoter region. Thus, the four genes of the six candidate transcriptional factors should be the novel transcriptional factors for RUNX1.

Academic Significance and Societal Importance of the Research Achievements

RUNX1は造血幹細胞の発生制御、血小板産生やT細胞分化に関わる転写因子であり、白血病発症にも深くかかわる。本研究によって、これまで知られていなかった6つのRUNX1発現に関わる転写因子を新規に特定することに成功した。これら転写因子群とRUNX1との機能協調の詳細な解析が進めば、RUNX1の分子メカニズムの解明へと展開するものと期待される。さらに、RUNX1の発現を細胞外から制御する方法を見出せれば、RUNX1を造血器疾患の新規分子標的療法の開発へも貢献することが期待される。

Report

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

    (10 results)

All 2022 2021 2020 2019

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

  • [Journal Article] Tumor necrosis factor-related apoptosis-inducing ligand is a novel transcriptional target of runt-related transcription factor 12022

    • Author(s)
      Yoshida Tatsushi、Yamasaki Kenta、Tadagaki Kenjiro、Kuwahara Yasumichi、Matsumoto Akifumi、Sofovic Adem、Kondo Noriko、Sakai Toshiyuki、Okuda Tsukasa
    • Journal Title

      International Journal of Oncology

      Volume: 60 Issue: 1 Pages: 1-1

    • DOI

      10.3892/ijo.2021.5296

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] C11orf21, a novel RUNX1 target gene, is down-regulated by RUNX1-ETO2022

    • Author(s)
      Matsumoto Akifumi、Yoshida Tatsushi、Shima Takahiro、Yamasaki Kenta、Tadagaki Kenjiro、Kondo Noriko、Kuwahara Yasumichi、Zhang Dong-Er、Okuda Tsukasa
    • Journal Title

      BBA Advances

      Volume: 2 Pages: 100047-100047

    • DOI

      10.1016/j.bbadva.2022.100047

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] A seaweed-derived compound that inhibits growth of acute myeloid leukemia cells.2021

    • Author(s)
      Tatsushi Yoshida, Kenjiro Tadagaki, Yasumichi Kuwahara, Tsukasa Okuda.
    • Organizer
      第80回日本癌学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 造血制御転写因子 RUNX1 標的遺伝子の解析2021

    • Author(s)
      吉田達士、山崎健太、忠垣憲次郎、桒原康通、近藤則子、松本晃典、酒井敏行、奥田司
    • Organizer
      第11回4大学連携研究フォーラム
    • Related Report
      2021 Annual Research Report
  • [Presentation] DNAメチル化プロファイルを用いたラブロイド腫瘍患者の同時多発病変より樹立した新規2細胞株の解析2020

    • Author(s)
      桒原康通、家原知子、勝見良樹、土屋邦彦、宮地充、田尻達郎、忠垣憲次郎、吉田達士、奥田司、細井創
    • Organizer
      第79回日本癌学会
    • Related Report
      2020 Research-status Report
  • [Presentation] クロマチンリモデリング因子研究におけるラブドイド腫瘍細胞株の有用性2020

    • Author(s)
      桒原康道、近藤則子、忠垣憲次郎、山崎健太、吉田達士、奥田司
    • Organizer
      第24回造血器腫瘍研究会
    • Related Report
      2019 Research-status Report
  • [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 Research-status Report
  • [Presentation] Analysis of a novel transcriptional target gene of RUNX1.2019

    • Author(s)
      Tatsushi Yoshida, Kenjiro Tadagaki, Yasumichi Kuwahara, Toshiyuki Sakai, Tsukasa Okuda.
    • Organizer
      第78回日本癌学会
    • Related Report
      2019 Research-status Report
  • [Presentation] Identification of a novel RUNX1 target by public data re-analysis that is suppressed by RUNX1-ETO.2019

    • 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
    • Related Report
      2019 Research-status 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、桒原康通、吉田達士、奥田司
    • Organizer
      第42回日本分子生物学会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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