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時空間的核アクチン重合化制御によるクロマチン構造と転写状態の変動

Publicly Offered Research

Project AreaDynamic chromatin structure and function
Project/Area Number 16H01321
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 InstitutionKindai University

Principal Investigator

宮本 圭  近畿大学, 生物理工学部, 講師 (40740684)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
Fiscal Year 2017: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2016: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Keywords核アクチン / リプログラミング / クロマチン構造 / 光遺伝学
Outline of Annual Research Achievements

カエル卵母細胞核内へと移植された哺乳類体細胞核は、卵由来のクロマチン結合タンパク質を取り込み、最終的に抑制遺伝子が活性される(転写のリプログラミング)。転写のリプログラミングは階層的なクロマチン構造の変化によって誘導されるのだが、核アクチンの重合化が重要な役割を果たしている可能性が示されてきた。そこで本研究では、光遺伝学の手法を用いて核アクチンの重合化を時空間特異的に制御し、核アクチンがクロマチン構造に与える影響並びにリプログラミングに果たす役割を明らかにする。
核アクチンの重合化を時空間的特異的に制御するために、光遺伝学ツールの一つである「LOV(light, oxygen, voltage)ドメイン」に注目した。LOVドメインにアクチン重合化促進因子であるRac1を結合することにより、Rac1のアクチン重合化活性が阻害されるが、光刺激に応答してRac1のアクチン重合化活性が復元する。これにより、リプログラミングを受けている最中の体細胞核に、核アクチン重合化を光刺激に応じて時期特異的に誘導することに成功し、アクチン重合化促進に反応してクロマチンへの結合が変化するタンパク質群を同定した。また、アクチン重合化促進の結果、体細胞クロマチンがゲノムワイドに弛緩した状態に変化することをATAC-seqにより示した。以上の結果より、リプログラミングを受ける核においてアクチン重合化を促進すると、クロマチンリモデリングが促進され、結果として弛緩した状態のクロマチンが作り上げられること明らかにした。
上記のカエル卵母細胞を用いた哺乳類体細胞核のリプログラミング系とは別に、マウス初期胚発生における核アクチン重合化の役割も調べ、核の膨化に核アクチン重合化が関与していることを明らかにした。

Research Progress Status

29年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

29年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (31 results)

All 2018 2017 2016 Other

All Int'l Joint Research (6 results) Journal Article (9 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 9 results,  Open Access: 8 results,  Acknowledgement Compliant: 3 results) Presentation (11 results) (of which Int'l Joint Research: 4 results,  Invited: 10 results) Remarks (4 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] ケンブリッジ大学(John Gurdon教授)(英国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] マーバーグ大学(Robert Grosse教授)(ドイツ)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] ブリストル大学(Abderrahmane Kaidi博士)(英国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] ケンブリッジ大学ガードン研究所/ブリストル大学(英国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] ニューヨーク大学アブダビ校(アラブ首長国連邦)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] マーバーグ大学(ドイツ)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Combinational treatment of Trichostatin A and vitamin C improves the efficiency of cloning mice by somatic cell nuclear transfer2018

    • Author(s)
      Azuma R, Miyamoto K, Oikawa M, Yamada M, Anzai M
    • Journal Title

      J Vis Exp.

      Volume: 134 Issue: 134 Pages: 1-10

    • DOI

      10.3791/57036

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Srf destabilizes cellular identity by suppressing cell-type-specific gene expression programs2018

    • Author(s)
      Ikeda T, Hikichi T, Miura H, Shibata H, Mitsunaga K, Yamada Y, Woltjen K, Miyamoto K, Watanabe A, Hiratani I, Yamada Y, Yamamoto T, Hotta A, Okita K, Masui S
    • Journal Title

      Nat Commun.

      Volume: 9 Issue: 1 Pages: 1387-1387

    • DOI

      10.1038/s41467-018-03748-1

    • NAID

      120006517799

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Peroxiredoxin as a functional endogenous antioxidant enzyme in pronuclei of mouse zygotes2018

    • Author(s)
      Morita K, Tokoro M, Hatanaka Y, Higuchi C, Ikegami H, Nagai K, Anzai M, Kato H, Mitani T, Taguchi Y, Yamagata K, Hosoi Y, Miyamoto K, Matsumoto K
    • Journal Title

      Journal of Reproduction and Development

      Volume: 64 Issue: 2 Pages: 161-171

    • DOI

      10.1262/jrd.2018-005

    • NAID

      130006699697

    • ISSN
      0916-8818, 1348-4400
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ubiquitin-proteasome system modulates zygotic genome activation in early mouse embryos and influences full-term development2018

    • Author(s)
      Higuchi C, Shimizu N, Shin SW, Morita K, Nagai K, Anzai M, Kato H, Mitani T, Yamagata K, Hosoi Y, Miyamoto K, Matsumoto K
    • Journal Title

      Journal of Reproduction and Development

      Volume: 64 Issue: 1 Pages: 65-74

    • DOI

      10.1262/jrd.2017-127

    • NAID

      130006405009

    • ISSN
      0916-8818, 1348-4400
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A transient pool of nuclear F-actin at mitotic exit controls chromatin organization2017

    • Author(s)
      Baarlink C, Plessner M, Sherrard A, Morita K, Misu S, Virant D, Kleinschnitz EM,Harniman R, Alibhai D, Baumeister S, Miyamoto K, Endesfelder U, Kaidi A, Grosse R
    • Journal Title

      Nat Cell Biol.

      Volume: 19 Issue: 12 Pages: 1389-1399

    • DOI

      10.1038/ncb3641

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Reprogramming towards totipotency is greatly facilitated by synergistic effects of small molecules2017

    • Author(s)
      Miyamoto K, Tajima Y, Yoshida K, Oikawa M, Azuma R, Allen GE, Tsujikawa T, Tsukaguchi T, Bradshaw CR, Jullien J, Yamagata K, Matsumoto K, Anzai M, Imai H, Gurdon JB, Yamada M
    • Journal Title

      Biology Open

      Volume: 6 Issue: 4 Pages: 415-424

    • DOI

      10.1242/bio.023473

    • NAID

      120006223660

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Gene Resistance to Transcriptional Reprogramming following Nuclear Transfer Is Directly Mediated by Multiple Chromatin-Repressive Pathways2017

    • Author(s)
      Jullien J, Vodnala M, Pasque V, Oikawa M, Miyamoto K, Allen G, David SA, Brochard V, Wang S, Bradshaw C, Koseki H, Sartorelli V, Beaujean N, Gurdon J
    • Journal Title

      Molecular Cell

      Volume: 65 Issue: 5 Pages: 873-884

    • DOI

      10.1016/j.molcel.2017.01.030

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Nuclear actin in development and transcriptional reprogramming2017

    • Author(s)
      Misu S, Takebayashi M, Miyamoto K
    • Journal Title

      Frontiers in Genetics

      Volume: 8 Pages: 27-27

    • DOI

      10.3389/fgene.2017.00027

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Sperm is epigenetically programmed to regulate gene transcription in embryos2016

    • Author(s)
      Teperek M, Simeone A, Gaggioli V, Miyamoto K, Allen GE, Erkek S, Kwon T, Marcotte EM, Zegerman P, Bradshaw CR, Peters AH, Gurdon JB, Jullien J
    • Journal Title

      Genome Research

      Volume: 26 Issue: 8 Pages: 1034-1046

    • DOI

      10.1101/gr.201541.115

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Roles of nuclear actin in mouse embryonic development2017

    • Author(s)
      宮本圭
    • Organizer
      2017年度生命科学系学会合同年次大会(ConBio2017)
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Nuclear actin polymerization in mouse embryonic development2017

    • Author(s)
      Miyamoto K
    • Organizer
      ASCB/EMBO 2017 meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 核の初期化とマウス初期胚発生における核アクチンの役割2017

    • Author(s)
      宮本圭
    • Organizer
      新学術領域研究・第5回公開シンポジウム
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Roles of nuclear actin in nuclear reprogramming and mouse embryonic development2017

    • Author(s)
      Miyamoto K
    • Organizer
      HMGU-Japan Epigenetics and Chromatin Symposium
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Open chromatin configuration at primed promoters is formed during embryogenesis and accelerates transcriptional activation during differentiation and nuclear reprogramming2017

    • Author(s)
      Miyamoto K
    • Organizer
      EMBO Conference The Nucleosome: From Atoms to Genomes
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Efficient nuclear reprogramming of somatic cells towards totipotency is supported by synergistic effects of small molecules2017

    • Author(s)
      Miyamoto K, Tajima Y, Yoshida K, Oikawa M, Azuma R, Mori M, Imasato Y, Allen G.E, Tsujikawa T, Tsukaguchi T, Bradshaw C.R, Jullien J, Yamagata K, Matsumoto K, Anzai M, Imai H, Gurdon J.B, Yamada M.
    • Organizer
      第50回 日本発生生物学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] The improved culture condition for mouse nuclear transfer embryos enables highly efficient nuclear reprogramming2016

    • Author(s)
      K. Miyamoto, Y. Tajima, K. Yoshida, T. Tsukaguchi, C.R. Bradshaw, G.E. Allen, M. Mori, Y. Imazato, J. Jullien, K. Matsumoto, H. Imai, J.B. Gurdon, and M. Yamada
    • Organizer
      The 3rd China-Japan-Korea reproduction meeting
    • Place of Presentation
      南京、中国
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Mechanisms of nuclear reprogramming in eggs and oocytes2016

    • Author(s)
      K.Miyamoto
    • Organizer
      King Abdullah University of Science and Technology
    • Place of Presentation
      アブドラ王立科学技術大学、サウジアラビア
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Mechanisms of nuclear reprogramming in eggs and oocytes2016

    • Author(s)
      K.Miyamoto
    • Organizer
      New York University Abu Dhabi
    • Place of Presentation
      ニューヨーク大学アブダビ校、UAE
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] クローン動物がもたらした可能性2016

    • Author(s)
      宮本圭
    • Organizer
      第109回日本繁殖生物学会大会
    • Place of Presentation
      麻布大学(神奈川県相模原市)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] アフリカツメガエル卵母細胞を用いたリプログラミングとクロマチン動構造の解析2016

    • Author(s)
      宮本圭
    • Organizer
      次世代両生類研究会
    • Place of Presentation
      基礎生物学研究所(愛知県岡崎市)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Remarks] Researchmap

    • URL

      https://researchmap.jp/KeiMiyamoto/?lang=japanese

    • Related Report
      2017 Annual Research Report
  • [Remarks] 動物におけるリプログラミング現象の解明から、細胞初期化の要素を特定する

    • URL

      http://top-researchers.com/?p=994

    • Related Report
      2017 Annual Research Report
  • [Remarks] Researchmap

    • URL

      http://researchmap.jp/KeiMiyamoto/

    • Related Report
      2016 Annual Research Report
  • [Remarks] Researchgate

    • URL

      https://www.researchgate.net/profile/Kei_Miyamoto/contributions

    • Related Report
      2016 Annual Research Report
  • [Patent(Industrial Property Rights)] 哺乳動物核移植胚の発生率向上法2017

    • Inventor(s)
      宮本圭、岩元正樹
    • Industrial Property Rights Holder
      (学)近畿大学、(株)プライムテック
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-015891
    • Filing Date
      2017-01-31
    • Related Report
      2016 Annual Research Report

URL: 

Published: 2016-04-26   Modified: 2022-02-28  

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