Regulation of H3K9me2 domain formation and higher order chromatin organization

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16049
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 43010:Molecular biology-related
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Fukuda Kei 国立研究開発法人理化学研究所, 開拓研究本部, 研究員 (00756786)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: ヘテロクロマチン / H3K9メチル化 / 高次クロマチン構造

Outline of Final Research Achievements

Heterochromatin, which is a transcriptionally inactive genomic region, is mainly modified by H3K9 methylation, and its abnormalities have been reported to be associated with various diseases such as cancer, infertility, and psychiatric disorders. In this study, in order to investigate the regulatory mechanism of H3K9 methylation, we analyzed the H3K9 methylation state, gene expression, and nuclear higher-order structure in mouse embryonic stem cells lacking each of the five types of H3K9 methylase in mammals. The results show that H3K9 methylation is regulated by different sets of H3K9 methylating enzymes depending on the intranuclear compartment, and that deficiency of H3K9 methylation alters the spatial arrangement of heterochromatin. Thus, we revealed that the regulation of H3K9 methylation and higher order chromatin organization have mutual relationship.

Free Research Field

ゲノム制御

Academic Significance and Societal Importance of the Research Achievements

転写不活性なゲノム領域であるヘテロクロマチンは主にH3K9メチル化により修飾されており、その異常はがん、不妊、精神疾患など様々な病気との関連が報告されている。本研究により、核内の空間配置によりH3K9メチル化が制御される機構が異なることがはじめて明らかになった。この研究成果はH3K9メチル化異常により生じる疾患の形成機序の理解につながると期待される。