Multiple functions of histone demethylases

2015 Fiscal Year Final Research Report

• Project/Area Number: 25640098
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Genome biology
• Research Institution: The University of Tokyo
• Principal Investigator: Inagaki Takeshi 東京大学, 先端科学技術研究センター, 特任准教授 (10507825)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: ヒストン修飾酵素 / ヒストン脱メチル化酵素 / ＪＭＪＤ１Ａ / 複合体形成 / ＨＤＡＣ / 転写 / ＦＢＸＬ１０

Outline of Final Research Achievements

JmjC domain is a demethylase signature motif and most of JmjC-containing-proteins work as histone demethylase. However, in this study, we demonstrated that JmjC-containing proteins also play non-enzymatic roles. Shotgun proteomic analysis using HeLa cells showed that JMJD1A binds to SIN3A complex including ARID1A and histone deacetylase (HDAC) 1. HDAC activity was induced by repressing Jmjd1a expression in multiple cell lines. Based on these findings, we speculated that JmjC-containing-proteins play non-enzymatic roles by forming functional complex to regulate gene expression. This notion is supported by our two findings that JMJD1A regulates chromatin dynamics by forming complex with SWI/SNF and PPARγ in brown adipocytes and that FBXL10 regulates white adipocyte differentiation by forming a novel polycomb repressive complex including RING1B, BCOR, and SKP1. In addition, our data suggested that JMJD1A regulates the expression of long non-coding RNA.

Free Research Field

生物学