Study on the regulatory mechanism of epigenome dynamics by histone modification erasers

2023 Fiscal Year Final Research Report

• Project Area: Mechanisms underlying replication of non-genomic codes that mediate plasticity and robustness for cellular inheritance
• Project/Area Number: 19H05742
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Hokkaido University
• Principal Investigator: MURAKAMI Yota 北海道大学, 理学研究院, 教授 (20260622)
• Project Period (FY): 2019-06-28 – 2024-03-31
• Keywords: ヘテロクロマチン / 反復配列 / 分裂酵母 / RNAi

Outline of Final Research Achievements

Eukaryotic DNA has a chromatin structure wrapped around histone proteins. Heterochromatin is defined by methylation of the 9th lysine of histone H3 (H3K9me) and suppresses gene expression, but it tends to form in DNA regions with repetitive sequences. However, the mechanism that connects repeat sequences and heterochromatin remains unclear. In this study, we reproduced this phenomenon in the model organism fission yeast and found that the Epe1 protein, which normally removes H3K9me, promotes H3K9me modification in repetitive DNA sequences via the RNAi mechanism. This proposes a new mechanism that connects heterochromatin and repetitive DNA sequences.

Free Research Field

分子生物学・エピジェネティクス

Academic Significance and Societal Importance of the Research Achievements

生物進化の過程でゲノムで繰り返し配列の増大がおこることが広く観察される。そして繰り返し配列は相同組み換えを介した遺伝子組換えの標的となりゲノム不安定性を招く。繰り返し配列上に形成されるヘテロクロマチンは遺伝子組換えを抑制し、ゲノム安定性に寄与すると考えられており、ヒトにおいてもその不具合によって発症する病気があることが知られている。しかし、反復配列上のヘテロクロマチン形成の分子機構は不明であった。したがって、本研究の成果は真核細胞のもつ根本的なゲノム安定性維持の仕組みの理解のみならず、今後ヒトにおける病気の治療法の探索にも有用であると考えられる。