Beyond allocating enhancers: Deciphering diverse roles of the ground-state chromatin conformation in gene regulation.

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K18454
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Genome biology
• Research Institution: The University of Tokyo
• Principal Investigator: Tsujimura Taro 東京大学, 医学部附属病院, 特任助教 (90741893)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: ゲノム / エンハンサー / クロマチン高次構造 / マウス / ゲノム編集

Outline of Final Research Achievements

I investigated diverse roles of the ground-state conformation of chromatin at a model locus of two adjacent genes Tfap2c and Bmp7. First, I introduced comprehensive deletions and inversions around the locus and analyzed their impact on the chromatin conformation. Notably, I found that an enhancer-like region that is active in a cell type specific manner is actively engaged in the organization of the chromatin conformation. Interestingly, changes of the ground-state conformation of chromatin upon the modification of the genome resulted in alteration of the interaction of the enhancer-like region. This finding highlights a novel mechanism of controlling enhancer activity by the ground-state conformation of chromatin.
Furthermore, I analyzed enhancer activity of the surrounding genomic regions of the locus in several cell types using in vitro and in vivo systems.

Free Research Field

ゲノム機能解析