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Regulation of gene expression program in the pluripotent embryos

Planned Research

Project AreaProgram of totipotency: From decoding to designing
Project/Area Number 19H05752
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 InstitutionThe University of Tokyo

Principal Investigator

Aoki Fugaku  東京大学, 大学院新領域創成科学研究科, 客員共同研究員 (20175160)

Project Period (FY) 2019-06-28 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥107,380,000 (Direct Cost: ¥82,600,000、Indirect Cost: ¥24,780,000)
Fiscal Year 2023: ¥20,540,000 (Direct Cost: ¥15,800,000、Indirect Cost: ¥4,740,000)
Fiscal Year 2022: ¥20,540,000 (Direct Cost: ¥15,800,000、Indirect Cost: ¥4,740,000)
Fiscal Year 2021: ¥22,490,000 (Direct Cost: ¥17,300,000、Indirect Cost: ¥5,190,000)
Fiscal Year 2020: ¥22,490,000 (Direct Cost: ¥17,300,000、Indirect Cost: ¥5,190,000)
Fiscal Year 2019: ¥21,320,000 (Direct Cost: ¥16,400,000、Indirect Cost: ¥4,920,000)
Keywords遺伝子発現プログラム / 全能性 / ヒストン変異体 / zygotic gene activation / Dux / Duxbl / 受精卵 / 着床前初期胚 / 胚性遺伝子活性化 / 初期発生 / 初期胚 / クロマチン構造 / リプログラミング / 転写因子 / DNA複製 / 着床前初期発生
Outline of Research at the Start

受精により全能性を有する1細胞期胚が生み出されるが、その際にそれまでの親世代の遺伝子発現プログラムが刷新され、新たに新世代のプログラムがスタートする。このプログラムは、発生を順調に進行させるために厳密に調節されていることが考えられるが、その実態はほとんど明らかにされていない。そこで、受精後に全能性を獲得した1細胞期胚からスタートする発生プログラムの完全理解に向けて、その基盤となる遺伝子発現プログラムの調節機構を明らかにする。

Outline of Final Research Achievements

The gene expression program after fertilization is initiated by the occurrence of minor zygotic gene activation (ZGA) and then followed by major ZGA. In this study, we clarified the mechanism regulating this process. We found that many Dux family genes are expressed soon after fertilization and then regulate the expression of major ZGA genes. The expression of Dux family genes is transient only during minor ZGA. The transition from minor ZGA to major one is regulated by the change in chromatin structure which is caused by the incorporation of H3.1/3.2, histone H3 variants, into chromatin.

Academic Significance and Societal Importance of the Research Achievements

現在、クローン動物やiPS細胞の作製成功により、再プログラム化ということに対して高い関心が寄せられている。すなわち、クローン動物やiPS細胞は現状では作成効率が極めて低く、その原因として再プログラム化がうまく成されていないことが考えられており、その改善に向けた研究が数多く行われている。しかし、再プログラム化を理解するためには、その元となるプログラムを理解することが必須である。そこで、本研究が端緒となり、プログラムの全容が解明されたら、その情報に基づいてリプログラミングが達成されない原因を究明し、その改善に向かうという新たなスキームが生まれるものと期待される。

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

    (23 results)

All 2023 2022 2021 2020 2019 Other

All Int'l Joint Research (1 results) Journal Article (9 results) (of which Peer Reviewed: 9 results,  Open Access: 6 results) Presentation (13 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results)

  • [Int'l Joint Research] University of Pennsylvania(米国)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Involvement of linker histone variant H1a in the regulation of early preimplantation development in mice2023

    • Author(s)
      FUNAYA Satoshi、WANG Yuan、SUZUKI Masataka G.、IKAWA Masahito、AOKI Fugaku
    • Journal Title

      Journal of Reproduction and Development

      Volume: 69 Issue: 3 Pages: 178-182

    • DOI

      10.1262/jrd.2023-013

    • ISSN
      0916-8818, 1348-4400
    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Involvement of the linker histone H1Foo in the regulation of oogenesis2022

    • Author(s)
      Satoshi Funaya, Yuria Kawabata, Kenta Sugie, Ken-Ichiro Abe, Yutaka Suzuki, Masataka G Suzuki, Fugaku Aoki
    • Journal Title

      Reproduction

      Volume: 164 Pages: 19-29

    • DOI

      10.1530/rep-21-0233

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cell cycle-dependent radiosensitivity in mouse zygotes2022

    • Author(s)
      Wang Yuan、Oda Shoji、Suzuki Masataka G.、Mitani Hiroshi、Aoki Fugaku
    • Journal Title

      DNA Repair

      Volume: 117 Pages: 103370-103370

    • DOI

      10.1016/j.dnarep.2022.103370

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Zygotic gene activation in mice: profile and regulation2022

    • Author(s)
      AOKI Fugaku
    • Journal Title

      Journal of Reproduction and Development

      Volume: 68 Issue: 2 Pages: 79-84

    • DOI

      10.1262/jrd.2021-129

    • NAID

      130008141670

    • ISSN
      0916-8818, 1348-4400
    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Asymmetrical deposition and modification of histone H3 variants are essential for zygote development2021

    • Author(s)
      Kawamura Machika、Funaya Satoshi、Sugie Kenta、Suzuki Masataka G、Aoki Fugaku
    • Journal Title

      Life Science Alliance

      Volume: 4 Issue: 8 Pages: e202101102-e202101102

    • DOI

      10.26508/lsa.202101102

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] dmrt11E ortholog is a crucial factor for oogenesis of the domesticated silkworm, Bombyx mori. Insect Biochem2021

    • Author(s)
      1.Kasahara R, Yuzawa T, Fujii T, Aoki F, Suzuki MG.
    • Journal Title

      Insect Biochem Mol Biol

      Volume: 129 Pages: 103517-103517

    • DOI

      10.1016/j.ibmb.2020.103517

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression of Dux family genes in early preimplantation embryos2020

    • Author(s)
      2.Sugie K, Funaya S, Kawamura M, Nakamura T, Suzuki MG, Aoki F
    • Journal Title

      Sci Rep

      Volume: 10 Issue: 1 Pages: 19396-19396

    • DOI

      10.1038/s41598-020-76538-9

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transgenic and knockout analyses of Masculinizer and doublesex illuminated the unique functions of doublesex in germ cell sexual development of the silkworm, Bombyx mori2020

    • Author(s)
      3.Yuzawa T, Matsuoka M, Sumitani M, Aoki F, Sezutsu H, Suzuki MG
    • Journal Title

      BMC Dev

      Volume: 20 Issue: 1 Pages: 19-19

    • DOI

      10.1186/s12861-020-00224-2

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulation of H3K9me3 during preimplantation development†2019

    • Author(s)
      Aoki Fugaku
    • Journal Title

      Biology of Reproduction

      Volume: 100 Issue: 1 Pages: 13-14

    • DOI

      10.1093/biolre/ioy201

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Presentation] Involvement of H2A variants in DNA damage response of zygotes2023

    • Author(s)
      Wang Y, Aoki F
    • Organizer
      Cold Spring Harbor Laboratory
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] H3.1/3.2 regulate the establishment of zygotic gene expression2023

    • Author(s)
      Funaya S, Aoki F
    • Organizer
      56th Annual meeting of Society for the Study of Reproduction
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 胚性遺伝子発現プログラムにおけるダブルホメオボックス遺伝子の役割2023

    • Author(s)
      青木不学
    • Organizer
      公開シンポジウム「全能性プログラム:デコーディングからデザインへ」
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Involvement of histone variants H3.1/3.2 in the progression of gene expression program in early mouse embryos2022

    • Author(s)
      Aoki F, Funaya S
    • Organizer
      The International Symposium "Totipotency and Germ Cell Development"
    • Related Report
      2022 Annual Research Report
  • [Presentation] マウス発生におけるH2A変異体の関与2021

    • Author(s)
      青木不学
    • Organizer
      全能性プログラム:デコーディングからデザインへ
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 受精前後における遺伝子発現リプログラミングに関する研究2021

    • Author(s)
      青木不学
    • Organizer
      第114回日本繁殖生物学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] マウス受精後における遺伝子発現リプログラミングへのH3.1/3.2の関与2021

    • Author(s)
      船屋智史,青木不学
    • Organizer
      第114回日本繁殖生物学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Cell-cycle phase dependent radiosensitivity of zygotes2021

    • Author(s)
      Yuan WANG, Fugaku AOKI
    • Organizer
      第114回日本繁殖生物学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] マウス着床前初期発生における遺伝子発現プログラムへのヒストン変異体H3.1/3.2の関与2020

    • Author(s)
      船屋智史、青木不学
    • Organizer
      第113回 日本繁殖生物学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 全能期における遺伝子発現プログラムの調節機構の解明2019

    • Author(s)
      青木不学
    • Organizer
      キックオフシンポジウム「全能性プログラム:デコーディングからデザインへ」
    • Related Report
      2019 Annual Research Report
  • [Presentation] 着床前初期胚におけるDux familyの発現とその機能2019

    • Author(s)
      杉江拳太、青木不学
    • Organizer
      第112回日本繁殖生物学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] マウス1細胞期胚のクロマチン構造へのリンカーヒストン変異体への関与2019

    • Author(s)
      船屋智史、青木不学
    • Organizer
      第112回日本繁殖生物学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Cell-cycle dependent response to DNA damage in mouse zygotes2019

    • Author(s)
      Yuan Wang、青木不学
    • Organizer
      第112回日本繁殖生物学会大会
    • Related Report
      2019 Annual Research Report

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

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