Elucidating mechano-sensing mechanisms by transcriptional machineries

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K20180
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 90110:Biomedical engineering-related
• Research Institution: Kyoto University
• Principal Investigator: Maki Koichiro 京都大学, 医生物学研究所, 助教 (90849233)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: バイオメカニクス / ＤＮＡ / 力学的構造変化

Outline of Final Research Achievements

Living tissues change their structure in response to mechanical loading. Cells are known to sense mechanical forces via mechanosensor molecules, but the mechanism by which gene expression is regulated under force remains unclear. In this study, we focused on chromatin in the cell nucleus to understand the effects of conformational changes in chromatin under force on gene expression. We believe that the separation of double-stranded DNA into single-stranded DNA is the key to understanding chromatin-mediated mechanosensing, and successfully constructed an experimental system to observe single-stranded DNA in the cell. In the future, we plan to verify whether mechanical forces in a cell induce the separation of double-stranded DNA into single-stranded DNA.

Free Research Field

バイオメカニクス

Academic Significance and Societal Importance of the Research Achievements

本研究では、in situ での一本鎖ＤＮＡの観察に世界で初めて成功した。これまで、ＤＮＡへの結合性を有した低分子の開発が行われてきたが、細胞内での妥当性の検討がボトルネックとなってきた。本研究では、細胞の semi-intact 化により、核酸への種々の酵素処理を可能とし、開発したイメージング手法における一本鎖ＤＮＡの検出の特異性を確認できた。一本鎖ＤＮＡと反応するタンパク質群に関して、今後幅広い探索が可能になることから、力のもとで生じるＤＮＡの構造変化を起点としたタンパク質構造体の形成・分解など、細胞の力感知機構を原点的に理解する足掛かりができた。