Formation of a Super-enhancer Loop Contributes to Transactivation of Cebpa Expression by PPARg during Adipocyte Differentiation

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09378
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: The University of Tokyo
• Principal Investigator: AOYAMA TOMOHISA 東京大学, 医学部附属病院, 助教 (50645538)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 糖尿病 / 肥満 / 脂肪細胞 / 遺伝子 / 転写制御 / 高次クロマチン構造 / ゲノム編集

Outline of Final Research Achievements

Adipogenesis is controlled by a cascade of transcription factors. The positive feedback loop established by the master regulators PPARγ and C/EBPα is considered to be crucial. Here, we performed ChIP-seq and identified a cluster of multiple distal PPARγ binding sites (+3, +19, +22, +24, +50, +53kb) in downstream region of the Cebpa gene in differentiated 3T3-L1 adipocytes. These clusters of enhancers showed high enrichment of Mediator complex binding and formed a super-enhancer. Furthermore, CTCF－a multifunctional insulator protein which mediates long-range chromatin looping－bound to both distal enhancers and the promoter. 4C-seq and 3C assays demonstrated formation of a chromatin loop encompassing the Cebpa promoter and the distal super-enhancer. Our findings suggest that PPARγ super-enhancer and CTCF-mediated loop formation are important for transactivation of Cebpa gene expression and differentiation.

Free Research Field

医歯薬学