Analysis of cohesin acetyltransferase on transcriptional regulation

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H04718
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Genome biology
• Research Institution: The University of Tokyo
• Principal Investigator: Bando Masashige 東京大学, 定量生命科学研究所, 助教 (90360627)
• Co-Investigator(Kenkyū-buntansha): 中戸 隆一郎 東京大学, 定量生命科学研究所, 助教 (60583044)
• Research Collaborator: Minamino Masashi ; Sakata Toyonori ; Yoshimura Atsunori ; Ishibashi Mai
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: コヒーシン / 転写制御 / アセチル化 / DNA複製 / ゲノム構造

Outline of Final Research Achievements

Cohesin regulates transcription through genome structure, but their detail molecular mechanisms are unknown. The dynamics of many proteins in the genome during the activation of transcription was analyzed using the in vitro assay system. And we observed the assembly of the cohesin loader, SEC, and ESCO1 in the addition of the preinitiation complex (PIC) on the template DNA. Cohesin loader was stably associated with PIC during the pausing. Moreover, the association of the cohesin loader and the SEC to the PIC may be competitive.
ESCO1 and ESCO2, unlike cohesin, were found to locally affect genome structure, resulting in changes in gene expression. In addition, we found a new mechanism in which ESCO2 is activated by binding to MCM and is degraded when it is dissociated from MCM.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

コヒーシンがゲノム構造を構築する重要な因子で、広く生理的な機能に重要な役割を担うことは知られているが、その詳細な機構についてはほとんど知られていない。本成果で用いたin vitroアッセイ系は、転写制御における分子機能に焦点を絞った解析を進めることができ、コヒーシン機能だけなく幅広い転写制御のメカニズムへの展開が期待される。また、本成果のESCOの機能や制御機構の理解は、コヒーシンと深く関わる癌や遺伝病の発症メカニズムの解明やその治療の標的分子として意義がある。