Deciphering the factors associated with selective demethylation of tissue-specific gene promoter

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K21142
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy; Applied molecular and cellular biology
• Research Institution: Osaka University
• Principal Investigator: Hino Nobumasa 大阪大学, 薬学研究科, 助教 (90469916)
• Research Collaborator: TAKASHIMA Seiji 大阪大学, 大学院生命機能研究科, 教授 ; OKADA Yoshiaki 大阪大学, 大学院薬学研究科, 准教授 ; KITA Ayami 大阪大学, 大学院薬学研究科, 大学院生
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: エピジェネティクス / 組織特異的遺伝子 / 脱メチル化 / タンパク質間相互作用 / 光クロスリンク / 非天然型アミノ酸

Outline of Final Research Achievements

Expression of tissue-specific gene is regulated by DNA methylation of its promoter region. The hypermethylated promoter is demethylated along with differentiation of the cells to induce the downstream gene expression. The demethylation is regulated by TET family enzymes (TET1-3), however, it is not well understood how these enzymes recognize promoters that should be demethylated at specific time point during cell differentiation. In this study, we attempted to identify TET1-interacting proteins that can recruit TET1 to specific promoter regions. We employed in vivo protein photo-cross-linking technique and identified a novel protein that binds to TET1 catalytic domain in living cells. Interestingly, the active form of this protein directly promoted the enzymatic activity of TET1 in vitro. Considered with the fact that this protein is activated during differentiation of several cell types, our findings suggest the existence of TET1-activity modulating mechanism at cell differentiation.

Free Research Field

分子生物学