Innovative Drug Development for Histone Methylase

2014 Fiscal Year Final Research Report

• Project/Area Number: 25670026
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: Osaka University
• Principal Investigator: DOI Takefumi 大阪大学, 薬学研究科(研究院), 教授 (00211409)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: ヒストンH３ / ヒストンメチル化 / SETDB1 / MCAF1 / 翻訳後修飾 / ユビキチン化

Outline of Final Research Achievements

SETDB1 is one of the H3K9 methylation enzymes and requires MCAF1 for H3K9’s tri-methylation. In this study, we have investigated the interaction between SETDB1 and MCAF1 to elucidate the tri-methylation mechanism by SETDB1.
We first confirmed that SETDB1(1-195) and MCAF1(562-817) formed a complex by immune-precipitation experiment. Then, in order to reveal the complex structure, we expressed these proteins in E.coli and purified them for further X-ray analysis.
Next, we searched the relationship between the post-translational modification and methylation activity of SETDB1. Analyses of several deletion mutants checking their methylation activities and modification revealed that the ubiquitination of SETDB1 is needed for its methylation activity.

Free Research Field

分子生物学