Elucidation of adipocyte-specific transcriptional regulation by analyzing three-dimensional chromatin interactions through Promoter Capture Hi-C method

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K16192
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• 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): 2018-04-01 – 2020-03-31
• Keywords: 脂肪細胞 / 転写制御 / 遠位エンハンサー / クロマチン3次元構造解析

Outline of Final Research Achievements

Adipogenesis is controlled by a cascade of transcription factors. Although the positive feedback loop established by the master regulators PPARγ and C/EBPα is considered to be crucial, the precise mechanism by which PPARγ regulates C/EBPα remains elusive. In this study, we analyzed unbiased genome-wide promoter-enhancer interactions in adipocytes by using Promoter Capture Hi-C which is a combination of the 3C method and high-throughput sequencing. In addition to the interaction between the C/EBPα promoter and the downstream distal region that we previously demonstrated in the 3C method, we identified novel interactions among the promotor and previously unrecognized genomic regions in the C/EBPα locus.

Free Research Field

代謝および内分泌学関連

Academic Significance and Societal Importance of the Research Achievements

次世代シークエンサーを用いた転写因子の結合領域やヒストン修飾領域のゲノムワイドな解析から、遺伝子発現の制御領域（エンハンサー）が遠位領域などゲノム上に広範囲に分布ことが明らかとなってきた。遠位エンハンサーは標的遺伝子のプロモーターとの間にクロマチンループを形成し、3次元空間上で近接して直接に相互作用することで発現制御を行うと考えられている。本研究はクロマチン3次元構造といった新しい視点からゲノムワイドにバイアスなく脂肪細胞特異的な遺伝子発現制御機構を解明する試みであり、新たな知見が得られることが期待される。