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

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08845
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Kyoto 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
• Keywords: 造血幹細胞 / 転写因子 / RUNX1 / 遺伝子発現制御 / プロモーター

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.

Free Research Field

生化学　分子生物学　腫瘍学　血液学

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。