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Evolutionary loss of regenerative ability: The role of evolutionary conserved regeneration signal-response enhancer

Research Project

Project/Area Number 16K07362
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Developmental biology
Research InstitutionYamagata University

Principal Investigator

Haruki Ochi  山形大学, 医学部, 准教授 (00505787)

Co-Investigator(Kenkyū-buntansha) 横山 仁  弘前大学, 農学生命科学部, 准教授 (90455816)
Research Collaborator SUZUKI Nanoka  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords非コードDNA / 再生シグナル応答エンハンサー / シス調節配列 / エンハンサー / 遺伝子発現制御 / エピゲノム / ネッタイツメガエル / アフリカツメガエル / ゲノム / 非コードDNA領域 / 再生 / 進化プロセス / 器官再生 / シス調節領域 / 再生シグナル / 発現制御 / 発生・分化 / 遺伝子 / 再生医学
Outline of Final Research Achievements

We screened regeneration signal-response enhancers (RSREs) at the lhx1 locus using a Xenopus transgenic system and found that the noncoding elements conserved between only highly regenerative species do not show strong enhancer activities in the regenerating amphibian nephric duct. Instead, the noncoding elements conserved from fish to humans function as enhancers in the regenerating nephric duct. We also found that DNA-binding motif of Arid3a, a component of H3K9me3 demethylases, was commonly found in RSREs. Arid3a is known as a component of H3K9 me3 demethylases KDM4/JMJD2 complex. Arid3a binds to RSREs and reduces the H3K9me3 levels on RSREs. It also promotes cell cycle progression and causes the outgrowth of nephric tubules, whereas the conditional knockdown of arid3a using photo-morpholino inhibits regeneration. These results suggest that Arid3a contributes to the regeneration of nephric tubules by decreasing H3K9me3 on RSREs.

Academic Significance and Societal Importance of the Research Achievements

進化の過程で両生類や魚類が再性能を獲得したのか、ほ乳類が再生能を失ったのか、これまでのところ、この問いに直接的な答えとなる分子実体を示した研究はなかった。一方で、ゲノムの比較解析と遺伝子の機能の解析からは、発生再生に関わる遺伝子は、その種類、数、機能が、進化的に高度に保存されていることが示されている。本研究により、再生を制御する遺伝子のみならず、その遺伝子の発現をオンにする調節配列も進化的に保存されていることと、その活性化メカニズムが明らかとなった。この発見は、ほ乳類においてその働きが抑制されていると予想されるシステムの解除による組織再生技術へと繋がる点において今後の発展の可能性が高い。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (23 results)

All 2019 2018 2017 2016 Other

All Journal Article (8 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 8 results,  Open Access: 8 results,  Acknowledgement Compliant: 2 results) Presentation (14 results) (of which Int'l Joint Research: 3 results,  Invited: 3 results) Remarks (1 results)

  • [Journal Article] Arid3a regulates nephric tubule regeneration via evolutionarily conserved regeneration signal-response enhancers2019

    • Author(s)
      Suzuki Nanoka、Hirano Kodai、Ogino Hajime、Ochi Haruki
    • Journal Title

      eLife

      Volume: 8

    • DOI

      10.7554/elife.43186

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reactivation of larval keratin gene (krt62.L) in blastema epithelium during Xenopus froglet limb regeneration.2017

    • Author(s)
      Satoh A, Mitogawa K, Saito N, Suzuki M, Suzuki KT, Ochi H, Makanae A.
    • Journal Title

      Developmental Biology

      Volume: 432 Issue: 2 Pages: 265-272

    • DOI

      10.1016/j.ydbio.2017.10.015

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Co-accumulation of cis-regulatory and coding mutations during the pseudogenization of the Xenopus laevis homoeologs six6.L and six6.S.2017

    • Author(s)
      Ochi H, Kawaguchi A, Tanouchi M, Suzuki N, Kumada T, Iwata Y, Ogino H.
    • Journal Title

      Developmental Biology

      Volume: 427 Issue: 1 Pages: 84-92

    • DOI

      10.1016/j.ydbio.2017.05.004

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Asymmetrically reduced expression of hand1 homeologs involving a single nucleotide substitution in a cis-regulatory element.2017

    • Author(s)
      Ochi, H., Suzuki, N., Kawaguchi, A. and Ogino, H.
    • Journal Title

      Dev. Biol.

      Volume: 425 Issue: 2 Pages: 152-160

    • DOI

      10.1016/j.ydbio.2017.03.021

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Conservatism and variability of gene expression profiles among homeologous transcription factors in Xenopus laevis.2017

    • Author(s)
      Watanabe, M., Yasuoka, Y., Mawaribuchi, S., Kuretani, A., Ito, M., Kondo, M., Ochi, H., Ogino, H., Fukui, A., Taira, M. and Kinoshita, T.
    • Journal Title

      Dev. Biol.

      Volume: 426 Issue: 2 Pages: 301-324

    • DOI

      10.1016/j.ydbio.2016.09.017

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genes coding for Cyclin-dependent Kinase Inhibitors are Fragile in Xenopus.2017

    • Author(s)
      Toshiaki Tanaka*, Haruki Ochi, Shuji Takahashi, Naoto Ueno, and Masanori Taira.
    • Journal Title

      Developmental Biology

      Volume: 印刷中 Issue: 2 Pages: 30055-0

    • DOI

      10.1016/j.ydbio.2016.06.019

    • NAID

      120006605591

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Genome evolution in the allotetraploid frog Xenopus laevis2016

    • Author(s)
      Session AM, Uno Y, Kwon T, Chapman JA, Toyoda A et al.
    • Journal Title

      Nature

      Volume: 538 Issue: 7625 Pages: 336

    • DOI

      10.1038/nature19840

    • NAID

      120006240046

    • URL

      https://pure.teikyo.jp/en/publications/7cb1b606-b88e-4144-9b58-280a85c3c635

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] A Novel Cysteine Knot Protein for Enhancing Sperm Motility That Might Facilitate the Evolution of Internal Fertilization in Amphibians.2016

    • Author(s)
      Yokoe M, Takayama-Watanabe E, Saito Y, Kutsuzawa M, Fujita K, Ochi H, Nakauchi Y, Watanabe A1
    • Journal Title

      PLoS One

      Volume: 11 Issue: 8 Pages: 1-13

    • DOI

      10.1371/journal.pone.0160445

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 再生シグナル応答エンハンサー ~活性化メカニズムと進化的保存性の意味~2019

    • Author(s)
      越智陽城
    • Organizer
      動物学会関東支部大会 公開シンポジウム 挑戦する両生類: カエル・イモリを使った研究の最前線 オーガナイザー
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] AT-rich interaction domain 3A regulates the regeneration of the nephric duct through the evolutionary conserved regeneration signal response enhancer2018

    • Author(s)
      Suzuki N, Ogino H, Ochi H
    • Organizer
      17th International Xenopus Conference
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Arid3a regulates the nephric tubule regeneration via the evolutionarily conserved regeneration signal-response enhancer2018

    • Author(s)
      Suzuki N, Hirano K, Ogino H, Ochi H
    • Organizer
      第12回日本ツメガエル研究集会・第4回次世代両生類研究会 合同シンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] ツメガエルを用いたゲノム進化研究とリソース事業について2018

    • Author(s)
      荻野肇, 田内幹大, 岩田 唯, 越智陽城, 井川武, 鈴木菜花, 柏木昭彦, 柏木啓子
    • Organizer
      第12回日本ツメガエル研究集会・第4回次世代両生類研究会 合同シンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] 局所的なshhの発現誘導によるXenopusの四肢のパターン形成への影響2018

    • Author(s)
      蓮潟里帆, 小林託也, 越智陽城, 田村宏治, 横山仁
    • Organizer
      再生学異分野融合研究会 (第1回)
    • Related Report
      2018 Annual Research Report
  • [Presentation] Xenopusの四肢再生における背腹軸形成機構の解析2018

    • Author(s)
      嶋田侑莉, 越智陽城, 横山仁
    • Organizer
      再生学異分野融合研究会 (第1回)
    • Related Report
      2018 Annual Research Report
  • [Presentation] The wild-type Xenopus laevis is an asymptomatic carrier of aniridia-like pax6 mutations2018

    • Author(s)
      Iwata Y, Tanouchi M, Igawa T, Sakagami K, Ochi H. Ogino H
    • Organizer
      51h Annual Meeting of the Japanese Society of Developmental Biologists
    • Related Report
      2018 Annual Research Report
  • [Presentation] The hypomorphic mutations hidden in the allotetraploid genome of Xenopus laevis2018

    • Author(s)
      Tanouchi M , Ochi H, Kawaguchi A, Igawa T, Iwata Y. Sakagami K, Ogino H
    • Organizer
      51h Annual Meeting of the Japanese Society of Developmental Biologists
    • Related Report
      2018 Annual Research Report
  • [Presentation] 腎組織再生におけるArid3aによる再生シグナル応答エンハンサーの活性化メカニズム.2017

    • Author(s)
      鈴木菜花, 熊田樹, 荻野肇, 越智陽城
    • Organizer
      第88回日本動物学会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 二倍体と四倍体のカエルのゲノムに刻まれたシス調節配列から遺伝子発現調節の進化を読み解く2017

    • Author(s)
      鈴木菜花, 熊田樹, 川口茜, 荻野肇, 越智陽城
    • Organizer
      第89回日本遺伝学会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] シス調節配列の1塩基置換による重複遺伝子の発現進化2016

    • Author(s)
      鈴木菜花, 熊田樹, 荻野肇, 越智陽城
    • Organizer
      第24回山形分子生物学セミナー
    • Place of Presentation
      山形大学農学部, 鶴岡市, 山形県
    • Year and Date
      2016-12-03
    • Related Report
      2016 Research-status Report
  • [Presentation] ゲノム編集ツールを使った両生類のコンディショナル遺伝子破壊法の確立2016

    • Author(s)
      熊田樹, 鈴木菜花, 平野高大, 越智陽城
    • Organizer
      第24回山形分子生物学セミナー
    • Place of Presentation
      山形大学農学部, 鶴岡市, 山形県
    • Year and Date
      2016-12-03
    • Related Report
      2016 Research-status Report
  • [Presentation] Single nucleotide substitution in cis-regulatory element causes asymmetrically reduced expression of hand1 homelogs in heart2016

    • Author(s)
      Ochi, H., Suzuki, S., Kawaguchi, A. and Ogino, H.
    • Organizer
      The 22nd International Congress of Zoology (ICZ),
    • Place of Presentation
      沖縄先端科学技術大学院大学, 沖縄コンベンションセンター, 宜野湾市, 沖縄, 日本
    • Year and Date
      2016-11-14
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Evolutionary conserved regeneration signal response enhancers for renal regeneration.,2016

    • Author(s)
      2.Suzuki, N., Kumada, T., Ogino, H. and Ochi H.
    • Organizer
      The 16th Xenopus international conference
    • Place of Presentation
      Orthodox Academy of Crete, Cania, Greece
    • Year and Date
      2016-08-28
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Remarks] 国立大学法人山形大学医学部 越智陽城研究室

    • URL

      http://ochi.yu-med-tenure.com/

    • Related Report
      2017 Research-status Report 2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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