Chromatin Dynamics and Epigenetic Regulation of Brown-Fat-Specific Transcription

2015 Fiscal Year Final Research Report

• Project/Area Number: 25293209
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: The University of Tokyo
• Principal Investigator: WAKI HIRONORI 東京大学, 医学部附属病院, 特任准教授 (00466765)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 褐色脂肪細胞 / 脂肪細胞 / エピゲノム / クロマチン / 遺伝子 / 転写制御 / 分化 / 肥満

Outline of Final Research Achievements

To gain insight into the underlying mechanism of brown fat development, we performed formaldehyde-assisted isolation of regulatory elements analysis coupled with high-throughput sequencing (FAIRE-seq) of murine brown adipose tissue (BAT) and white adipose tissue (WAT). Through motif analysis of BAT-specific open chromatin regions and expression analysis, we identified NFIA as a novel regulator of brown adipocyte differentiation. Using cell culture, NFIA knockout mice, and chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq), we demonstrated that NFIA controls the BAT-specific gene program by activating the cell-type-specific enhancers and facilitating the binding of the adipogenic master regulator, PPARγ.

Free Research Field

糖尿病・代謝内科学