Analysis of molecular mechanism regulating enzyme function of histone methylation enzyme SETDB1

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H04644
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Osaka University
• Principal Investigator: DOI Takefumi 大阪大学, 薬学研究科, 教授 (00211409)
• Co-Investigator(Kenkyū-buntansha): 井上 豪 大阪大学, 工学研究科, 教授 (20263204) ; 橘 敬祐 大阪大学, 薬学研究科(研究院), 招へい教員 (30432446)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: ヒストンメチル化 / 翻訳後修飾 / ユビキチン化

Outline of Final Research Achievements

Molecular mechanisms that control the enzymatic function of SETDB1, an enzyme that specifically methylates histone H3K9, were analyzed by a multiple approach. (1) We demonstrated that mono-ubiquitination modification of SETDB1 regulates gene expression via H3K9me3 activity. In addition, TRIM28, a chromatin regulator, was identified as a factor related to its regulatory mechanism. (2) SETDB1 in the nucleus showed stable expression by proteasome inhibitor and nuclear export inhibitor, and ligase X was found as a candidate factor related to it. (3) In order to conduct X-ray crystal structure analysis of SETDB1-MCAF1, we performed protein purification and its crystallization. The novel finding of SETDB1 clarified in this research leads to the development of new cancer therapeutic drug targeting SETDB1.

Free Research Field

生物系薬学、分子生物学