Revealing aging-associated chromatin structural change at the nucleosome level

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K05512
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 38060:Applied molecular and cellular biology-related
• Research Institution: Kyoto University (2023); Institute of Physical and Chemical Research (2021-2022)
• Principal Investigator: Ohno Masae 京都大学, 高等研究院, 特定講師 (10581738)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ヌクレオソーム / ゲノム構造 / 染色体立体配座捕捉法

Outline of Final Research Achievements

Revealing chromatin structure is a key for understanding genomic function including transcription. In this study, we attempt to capture chromatin structural changes associated with yeast aging by using our developed chromatin structural analysis, Hi-CO. We here used yeast cells in exponential growth phase as pre-senescent cells and yeast cells in stationary-phase as senescent cells. Our Hi-CO can reveal nucleosome folding in these cells by detecting spatial proximity among nucleosomes. We showed that nucleosome interactions in promoter regions were significantly changed before and after senescence. We also found that these structural changes are associated with gene expression. These results suggest that local nucleosome folding at promoter regions is involved in the changes in gene expression associated with aging.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

細胞老化の分子メカニズムの解明は、古くから行われている重要な研究テーマである。しかし、老化過程に伴うゲノム構造変化、特に、ヌクレオソームや遺伝子レベルでのゲノム構造変化の解明はあまり進んでいない。この問題を解決するため、本研究では申請者が開発したHi-CO法を用いて、老化に伴う前後のゲノム構造をヌクレオソームレベルで明らかにすることを目指した。その結果、本研究により、老化に伴うゲノム構造変化、特に、プロモーター領域のヌクレオソーム高次構造変化をとらえることに成功した。本研究により、老化に伴う遺伝子発現変化とゲノム構造の関係の一端を明らかにした。