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Mechanism of chromatin higher-order structural conversion during meiosis initiation in mammalian germ cells

Research Project

Project/Area Number 19K06642
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 44010:Cell biology-related
Research InstitutionKumamoto University

Principal Investigator

Takada Yuki  熊本大学, 発生医学研究所, 助教 (40392013)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords哺乳類 / 減数分裂 / コヒーシンタンパク質 / インスレータータンパク質 / クロマチン / コヒーシン タンパク質 / クロマチン高次構造 / インスレーター結合タンパク質
Outline of Research at the Start

減数第一分裂期では、体細胞分裂期にある細胞とは異なった、特有の染色体動態及び構造変換が認められる。しかし、体細胞分裂を行う生殖幹細胞から、減数分裂期にある生殖細胞への遷移期の複雑な染色体の挙動と、それに伴った核内クロマチン高次構造のスイッチング機構には不明な点が多い。
本研究では、マウスにおける減数分裂型インスレーターおよびコヒーシンタンパク質それぞれの相互作用因子及び生殖細胞核内における結合領域を同定することにより、生殖細胞系列におけるクロマチン高次構造のスイッチング機構を明らかにする。

Outline of Final Research Achievements

The aim of this study is to elucidate the mechanism of nuclear chromatin higher-order structural conversion from somatic to meiotic lineages in mammals. In meiosis I, specific chromosomal dynamics and structural transformations are observed, which are different from those of cells in somatic cell division. However, the complex behavior of chromosomes during the transition from somatic to meiotic germ cells and the associated conversion mechanisms of nuclear chromatin higher-order structures are still unknown. In this study, we focus on meiotic insulator and cohesin proteins to elucidate this mechanism by identifying for their interaction factors and genome-wide analysis of their binding regions to the genome in the germ cell nucleus.

Academic Significance and Societal Importance of the Research Achievements

体細胞分裂により増殖した生殖幹細胞が減数分裂期へエントリーする遷移期の複雑な染色体の挙動と、それに伴う核内クロマチン高次構造のスイッチング機構には不明な点が多い。解析対象となる細胞集団が生体内においてごく少数であることから、我々は高い純度で効率よくサンプルを確保する手法を確立し、さまざまなアプリケーションに対応できるようにできたことは非常に大きい進歩である。本研究課題による成果をもとにした基礎医学的な理解が、社会問題となっているヒトの不妊疾患の原因究明や創薬・治療法確立の基盤になると考えている。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (3 results)

All 2021 2020

All Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 3 results,  Open Access: 2 results)

  • [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] Maintenance DNA methylation in pre-meiotic germ cells regulates meiotic prophase by facilitating homologous chromosome pairing2021

    • Author(s)
      Takada Yuki、Yaman-Deveci Ruken、Shirakawa Takayuki、Sharif Jafar、Tomizawa Shin-ichi、Miura Fumihito、Ito Takashi、Ono Michio、Nakajima Kuniko、Koseki Yoko、Shiotani Fuyuko、Ishiguro Kei-ichiro、Ohbo Kazuyuki、Koseki Haruhiko
    • Journal Title

      Development

      Volume: 148 Issue: 10

    • DOI

      10.1242/dev.194605

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Meiotic cohesins mediate initial loading of HORMAD1 to the chromosomes and coordinate SC formation during meiotic prophase2020

    • Author(s)
      Fujiwara Yasuhiro、Horisawa-Takada Yuki、Inoue Erina、Tani Naoki、Shibuya Hiroki、Fujimura Sayoko、Kariyazono Ryo、Sakata Toyonori、Ohta Kunihiro、Araki Kimi、Okada Yuki、Ishiguro Kei-ichiro
    • Journal Title

      PLOS Genetics

      Volume: 16 Issue: 9 Pages: e1009048-e1009048

    • DOI

      10.1371/journal.pgen.1009048

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research

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Published: 2019-04-18   Modified: 2023-01-30  

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