Analysis of Inheritance Mechanism of Transcription Factor Networks in Chromatin Replication

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: 19H05748
• 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: Kumamoto University
• Principal Investigator: Niwa Hitoshi 熊本大学, 発生医学研究所, 教授 (80253730)
• Project Period (FY): 2019-06-28 – 2024-03-31
• Keywords: 転写因子ネットワーク / 細胞複製 / 細胞周期

Outline of Final Research Achievements

Using mouse ES cells, we analyzed the mechanism by which transcription factor network activity regulating gene expression is inherited through cell division. The repli-ATAC-seq analysis of transcription factor binding to the S-phase nascent strand revealed that KLF2/4/5-mediated activation of distal enhancer and the resulting change in accessibility of the promoter region associated with the change in gene expression play an important role in the restructuring of transcriptional network activity after DNA replication. We also identified Dppa2 as a novel M-phase chromosome-binding transcription factor, which antagonizes the PCGF6-PRC1 polycomb group complex to regulate novel methylation of target genes.

Free Research Field

幹細胞生物学

Academic Significance and Societal Importance of the Research Achievements

細胞が分裂を経て同じ表現型の細胞を生み出すためには、特定の遺伝子発現パターンを規定する転写因子ネットワークの活性が継承される必要がある。本研究では、転写因子ネットワークに含まれる特定の転写因子が、この過程に重要な役割を果たすことが示唆された。このような制御機構には普遍性があることが想定されるので、基礎生物学の進展と、細胞工学的分化転換技術の理解と改良に寄与する地検になると考えられる。