The roles of histone demethylases in transcriptional process involved in cell differentiation

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K06492
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43010:Molecular biology-related
• Research Institution: Keio University
• Principal Investigator: Akiyama Tomohiko 慶應義塾大学, 医学部(信濃町), 講師 (20570691)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 多能性 / 転写制御因子 / 配置制御

Outline of Final Research Achievements

In this study, we found that UTX regulates pluripotency of human ES cells by the demethylase activity independent pathway. Therefore, we focused on UTY, a homolog of UTX, which is encoded on the Y chromosome. UTY is evolutionarily mutated in the enzyme activity and has no demethylation function. When both UTX and UTY were deleted, abnormalities in gene expression were observed globally in undifferentiated ES cells and differentiated cells. Furthermore, the localization of transcription factors that bind to enhancer regions was altered in thousands of locations. These results indicate that UTX and UTY regulate transcription factor positioning in a demethylase-independent manner and are involved in the regulation of ES cell differentiation.

Free Research Field

幹細胞制御

Academic Significance and Societal Importance of the Research Achievements

本研究では、ヒト多能性幹細胞における転写制御因子のゲノム上の配置を制御する因子を同定した。これらの結果は、ヒト発生の分子機構を明らかにしただけでなく、細胞分化誘導技術の開発において有用な知見として期待される。