The function of histone demethylase JMJD1A as a signal-sensing scaffold

2017 Fiscal Year Final Research Report

• Project/Area Number: 25291002
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Molecular biology
• Research Institution: Gunma University (2016-2017); The University of Tokyo (2013-2015)
• Principal Investigator: INAGAKI TAKESHI 群馬大学, 生体調節研究所, 教授 (10507825)
• Co-Investigator(Renkei-kenkyūsha): SAKAI JURO 東京大学, 先端科学技術研究センター, 教授 (80323020) ; ABURATANI HIROYUKI 東京大学, 先端科学技術研究センター, 教授 (10202657) ; FUJITA TOSHIRO 東京大学, 先端科学技術研究センター, 特任研究員 (10114125) ; KAWAMURA TAKESHI 東京大学, アイソトープ総合センター, 准教授 (70306835)
• Project Period (FY): 2013-04-01 – 2018-03-31
• Keywords: エピゲノム / クロマチン構造 / ヒストン脱メチル化酵素 / JMJD1A / 熱産生 / 褐色脂肪

Outline of Final Research Achievements

Regulating metabolic diseases including diabetes mellitus and obesity is an important research issue for human health. We previously elucidated that the mouse lucking histone demethylase JMJD1A is obesity, diabetes, and cold-sensitive. In this study, we elucidated that JMJD1A is phosphorylated at S265 by β-adrenergic stimulation in response to acute cold exposure. Phosphorylated JMJD1A forms complex with SWI/SNF chromatin remodeler and nuclear transcription factor PPARγ. The P-JMJD1A-SWI/SNF-PPARγ complex induces enhancer-promoter proximity by forming long-range chromatin loop and, in turn, regulates thermogenic gene expression. Thus, phosphorylated histone demethylase JMJD1A regulates metabolic gene expression by mediating long-range genomic interactions in response to β-adrenergic stimulation.

Free Research Field

生物学