unraveling an epigenetic system by targeting a novel metabolite sensor.

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K19889
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Health science and related fields
• Research Institution: University of Tsukuba
• Principal Investigator: Sekiya Motohiro 筑波大学, 医学医療系, 准教授 (50420245)
• Project Period (FY): 2017-06-30 – 2020-03-31
• Keywords: 代謝産物 / センサー / エピゲノム

Outline of Final Research Achievements

We investigated the role of CtBP2 in epigenomic transcriptional regulation mainly by focusing on pancreatic beta cells, where activation of CtBP2 opened the chromatin archtecture by changing histone modifications represented by H3K4me2, H3K4me3, H3K9, H3H27ac and H3K27me.
We further generated pancreatic beta-cell specific CtBP2 knockout mice that showed impaired insulin secretion consistent with these findings.
We are currently analyzing mice lacking the metabolite-sensing pocket in CtBP2.

Free Research Field

代謝学

Academic Significance and Societal Importance of the Research Achievements

CtBP2の代謝産物センシング機構、およびそのポケット構造は代謝疾患治療薬として標的に出来ることが申請者らの研究でわかってきており、今回の研究もそれをさらに裏付けるものとなっている。
新しい機序の治療薬開発に向けた準備の意義が大きい。