Epigenetic regulation of circadian rhythm in HepG2 cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K05719
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 37010:Bio-related chemistry
• Research Institution: National Institute of Advanced Industrial Science and Technology
• Principal Investigator: TOMITA Tatsunosuke 国立研究開発法人産業技術総合研究所, 生命工学領域, 主任研究員 (60415718)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 時計遺伝子 / エピゲノム

Outline of Final Research Achievements

We investigated the effect of azaC treatment on the recovery mechanism of clock gene expression rhythm in HepG2 cells. Using DNA microarray and qPCR, we examined the expression changes of clock genes, but no significant expression changes dependent on the treatment period were observed. Additionally, methylation analysis of the promoter regions of Bmal1 and Per2 did not show significant changes, suggesting no direct impact of methylation. On the other hand, a DNA topoisomerase, which has been reported to be involved in rhythm regulation, showed a significant increase in expression. This suggests its important role. Further analysis will be conducted to elucidate the mechanism of clock gene rhythm recovery in HepG2 cells through azaC treatment.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

体内時計のリズムを示さないHepG2の細胞においても、DNAメチル化解除試薬である5-azaCを長期間低濃度で曝露することにより、リズムの発現が回復することが分かった。このことは、元来HepG2に備わっていたリズム発振機構が、培養方法を工夫することによって、発現することを示した結果である。時計遺伝子のリズムは様々な遺伝子の発現を調節しており、これまで言われていたHepG2の肝臓らしい機能の欠損をリズムの回復を通じて、回復できるかの検討を進める糸口となる成果である。