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Analysis of Inheritance Mechanism of Transcription Factor Networks in Chromatin Replication

Planned Research

Project AreaMechanisms 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 TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionKumamoto 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
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥100,490,000 (Direct Cost: ¥77,300,000、Indirect Cost: ¥23,190,000)
Fiscal Year 2023: ¥20,540,000 (Direct Cost: ¥15,800,000、Indirect Cost: ¥4,740,000)
Fiscal Year 2022: ¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2021: ¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Fiscal Year 2020: ¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Fiscal Year 2019: ¥25,740,000 (Direct Cost: ¥19,800,000、Indirect Cost: ¥5,940,000)
Keywords転写因子ネットワーク / 細胞複製 / 細胞周期 / ES細胞 / 転写因子 / DNA複製
Outline of Research at the Start

本計画研究においては、新学術領域の連携を生かし、DNA 複製ならびに細胞分裂に伴い、転写因子はどのようにゲノムへの結合を回復し、転写因子ネットワーク活性を維持するのか、ないしはそれを遷移させ細胞を分化させるのか、鍵になる転写因子を同定し、その機能を明らかにすることを、(1)ゲノム複製と転写因子ネットワーク活性をつなぐ分子機構の解析、(2)細胞分裂と転写因子ネットワーク活性をつなぐ分子機構の解析、により目指すものである。

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.

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。

Report

(6 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (6 results)

All 2023 2022 2021 2020

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 4 results)

  • [Journal Article] The role of <i>Zfp352</i> in the regulation of transient expression of 2‐cell specific genes in mouse embryonic stem cells2023

    • Author(s)
      Mwalilino Lusubilo、Yamane Mariko、Ishiguro Kei‐ichiro、Usuki Shingo、Endoh Mitsuhiro、Niwa Hitoshi
    • Journal Title

      Genes to Cells

      Volume: 28 Issue: 12 Pages: 831-844

    • DOI

      10.1111/gtc.13070

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The polyol pathway is an evolutionarily conserved system for sensing glucose uptake.2022

    • Author(s)
      *Sano, H., Nakamura, A., Yamane, M., Niwa, H., Nishimura, T., Takemoto, K., Ishiguro, K., Aoki, H., Kato, Y., and Kojima, M.
    • Journal Title

      PLOS Biology

      Volume: 20 Issue: 6 Pages: 1-25

    • DOI

      10.1371/journal.pbio.3001678

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Stepwise pluripotency transitions in mouse stem cells2022

    • Author(s)
      Mitsuhiro Endoh, Hitoshi Niwa
    • Journal Title

      EMBO Reports

      Volume: 23 Issue: 9

    • DOI

      10.15252/embr.202255010

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Meiosis-specific ZFP541 repressor complex promotes developmental progression of meiotic prophase towards completion during mouse spermatogenesis2021

    • Author(s)
      Horisawa-Takada Yuki et al.
    • Journal Title

      Nature Communications

      Volume: 12 Issue: 1 Pages: 3184-3184

    • DOI

      10.1038/s41467-021-23378-4

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] MEAF6 is essential for cell proliferation and plays a role in the assembly of KAT7 complexes2020

    • Author(s)
      Matsuura Kumi、Tani Naoki、Usuki Shingo、Torikai-Nishikawa Satomi、Okano Masaki、Niwa Hitoshi
    • Journal Title

      Experimental Cell Research

      Volume: 396 Issue: 1 Pages: 112279-112279

    • DOI

      10.1016/j.yexcr.2020.112279

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] MEIOSIN directs the switch from mitosis to meiosis in mammalian germ cells2020

    • Author(s)
      Ishiguro K* (Corresponding), Matsuura K, Tani N, Takeda N, Usuki S, Yamane M, Sugimoto M, Fujimura S, Hosokawa M, Chuma S, Ko S.H.M, Araki K, Niwa H
    • Journal Title

      Dev. Cell

      Volume: 52 Issue: 4 Pages: 429-445

    • DOI

      10.1016/j.devcel.2020.01.010

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed

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Published: 2019-07-04   Modified: 2025-01-30  

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