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2021 Fiscal Year Final Research Report

Functional analyses of enzymatic activity- and complex formation-dependent roles of UTX in the regulation of hematopoietic stem cells and development of hematopoietic diseases

Research Project

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Project/Area Number 19H03693
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 54010:Hematology and medical oncology-related
Research InstitutionTokyo Women's Medical University

Principal Investigator

HONDA HIROAKI  東京女子医科大学, 医学部, 教授 (40245064)

Co-Investigator(Kenkyū-buntansha) 世良 康如  東京女子医科大学, 医学部, 助教 (40836532)
本田 善一郎  お茶の水女子大学, 保健管理センター, 特任教授 (70238814)
中田 雄一郎  広島大学, 原爆放射線医科学研究所, 助教 (90793430)
Project Period (FY) 2019-04-01 – 2022-03-31
KeywordsUTX / ヒストン修飾因子 / 脱メチル化活性 / 造血幹細胞 / 造血器腫瘍 / UTY
Outline of Final Research Achievements

To analyze demethylase-dependent and -independent roles of UTX, a histone modifier, in hematopoiesis, we generated mice which express wild-type UTX at steady-state and inducibly express a UTX mutant lacking its demethylase activity (DD) or a UTX mutant lacking its protein-binding domain (ΔTPR). We analyzed the expression of DD or ΔTPR in hematopoietic cells after induction, but we could not detect obvious expression of both proteins. This suggests the possibilities that 1) induction efficiency is not high enough or 2) hematopoietic cells expressing DD or ΔTPR can hardly survive, and we are currently analyzing both possibilities.
In addition, since UTX exists on the X chromosome, we also generated mice lacking UTY, the Y chromosome homologue of UTX. Mice lacking UTY were normally born and we confirmed the absence of UTY protein.

Free Research Field

血液内科学

Academic Significance and Societal Importance of the Research Achievements

ヒストン修飾因子UTXは白血病を含む悪性腫瘍で変異を認めるが、脱メチル化活性依存性、非依存性のどちらが重要であるかは不明である。この問題を解決する目的で、我々は誘導可能に脱メチル化活性を欠失したUTX変異体(DD)または蛋白質結合部位を欠失したUTX変異体(ΔTPR)を発現するマウスを作製した。しかし、造血細胞を用いた解析ではDD、ΔTPRの発現は認められず、造血細胞機能や造血器腫瘍発症における脱メチル化活性の役割は今後の課題と考えられる。また、UTXはX染色体に存在するためY染色体における相補体UTYの欠失マウスも作製した。このUTY欠損マウスは、UTYの機能解析に有用なモデルと期待される。

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Published: 2023-01-30  

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