Mechanism of HP1-mediated heterochromatin formation in mammals

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K15067
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 43050:Genome biology-related
• Research Institution: Osaka University
• Principal Investigator: Maeda Ryo 大阪大学, 大学院生命機能研究科, 特任助教(常勤) (90814575)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: ヘテロクロマチン / H3K9メチル化

Outline of Final Research Achievements

Constitutive heterochromatin (heterochromatin) is required for the regulation of gene expression to define the uniqueness of cells. However, the molecular mechanism underlying heterochromatin formation remains unclear. Heterochromatin is formed by the binding of HP1 to histone modification H3K9 methylation. Thus, we generated mouse ES cells lacking HP1 and analyzed the role of HP1 on methyltransferases, and found that HP1 is involved in the formation of heterochromatin by promoting protein stability of H3K9 methyltransferases and demethylases. These findings were published in EMBO Rep.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究成果により、HP1とH3K9メチル化酵素・脱メチル化酵素の結合が、これらの酵素の安定化に必須であることが明らかとなった。早期老化症やがんなどのさまざまな疾患でH3K9メチル化の異常は観察される。これらの酵素とHP1の結合領域に入り結合を阻害、あるいは促進する薬物を開発することで、H3K9メチル化の異常が原因で引き起こされる疾患に対する治療法を提案できる可能性がある。