Mechanism of DNA loop formation by osmotic pressure of cohesin

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K03558
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 13040:Biophysics, chemical physics and soft matter physics-related
• Research Institution: Hokkaido University (2019-2020); Nagoya University (2018)
• Principal Investigator: Yamamoto Tetsuya 北海道大学, 化学反応創成研究拠点, 特任准教授 (40610027)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: ループ押し出し / スーパーエンハンサ / 転写凝集体 / 転写ダイナミクス

Outline of Final Research Achievements

DNA in eukaryotic cells is composed of DNA loops of the order of 10k-1Mbps. The DNA loops are produced by the loop extrusion process, with which cohesin uni-directionally translocates DNA with a constant rate. With cohesin removal, the transcription levels of the target genes of superenhancers decreases significantly. The superenhancers are localized at the surfaces of transcriptional condensates, which are composed of transcriptional machineries. We have analyzed the dynamics of DNA at the surfaces of transcriptional condensates to theoretically predict that the loop extrusion process decreases the surface tension of transcriptional condensates and enhances the accessibility of the target genes of superenhancers to the transcriptional machineries in the condensates.

Free Research Field

転写制御の物理

Academic Significance and Societal Importance of the Research Achievements

多細胞生物は、様々な種類の細胞から構成されていますが、どの細胞も同じDNA（設計図）から形成されています。設計図は転写と呼ばれる過程によって読み取られますが、私の研究は、DNAの中で読み取られる部分と読み取られない部分が決定される機構（遺伝子制御機構）を物理を用いて明らかにするものです。本研究課題は、DNAの構造形成に重要な分子であるコヒーシンが、DNAの読み取り頻度に与える影響を理論的に調べたもので、遺伝子制御の物理を作るための重要なピースです。