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Cross-species study of unsolved structure and function of human ultraconserved elements

Research Project

Project/Area Number 16K07463
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Evolutionary biology
Research InstitutionKyoto Institute of Technology

Principal Investigator

Takano Toshiyuki  京都工芸繊維大学, 応用生物学系, 教授 (90202150)

Co-Investigator(Kenkyū-buntansha) 都丸 雅敏  京都工芸繊維大学, 応用生物学系, 助教 (70324720)
Research Collaborator Ohsako Takashi  
Timothy Karr  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords超保存配列 / ショウジョウバエ / 遺伝子発現制御 / エンハンサー / 生物種横断研究 / サイレンサー / インスレーター / 遺伝子発現調節 / 進化
Outline of Final Research Achievements

Comparative genomics has identified a large number of non-coding segments that have been highly conserved over hundreds of millions of years of vertebrate evolution (so-called ultra-conserved elements, UCE). To examine their functions in vivo, we generated over 400 Drosophila transgenic lines, each containing a unique human non-coding ultra-conserved element inserted upstream of a core promoter fused to a GAL4 gene, and then assessed their enhancer activities. We observed reporter GFP expression in one or more tissues of larvae or adults in all tested elements, implying that human ultra-conserved elements can function as enhancer in Drosophila. Most of the elements studied induced GFP expression in larval CNS, whereas no UCE induced expression in adult testis. The findings suggest that the transcriptional environment of testis cells significantly differs between human and fly. Alternatively, but not mutually exclusive, the UCEs may function specifically in brain.

Academic Significance and Societal Importance of the Research Achievements

超保存配列は、遺伝子をコードする領域だけでなく、非コード領域にも存在し、遺伝子発現の制御に関わることが示唆されている。しかし、実際にマウス等をつかってエンハンサー活性が実証されたのは約半数にとどまる。本研究によって、はじめて超保存配列のそのすべてがエンハンサー活性を有することが明らかになった。また、エンハンサー活性の組織特異性は細胞内環境の保存性の違いを示唆する。脳と違って、精巣の発現制御の環境は速く進化しているのかもしれない。

Report

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

    (20 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (1 results) Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 2 results) Presentation (12 results) (of which Int'l Joint Research: 5 results,  Invited: 4 results) Book (2 results)

  • [Int'l Joint Research] Baylor College of Medicine/Lawrence Berkeley National Laboratory(米国)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Cortex glia clear dead young neurons via Drpr/dCed-6/Shark and Crk/Mbc/dCed-12 signaling pathways in the developing Drosophila optic lobe.2019

    • Author(s)
      Nakano, R., Iwamura, M., Obikawa, A., Togane, Y., Hara, Y., Fukuhara, T., Tomaru, M., Takano, T., and Tsujimura H.
    • Journal Title

      Developmental Biology

      Volume: 印刷中 Issue: 1 Pages: 68-85

    • DOI

      10.1016/j.ydbio.2019.05.003

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Normal aging hyperactivates innate immunity and reduces the medical efficacy of minocycline in brain injury.2019

    • Author(s)
      Sanuki, R., Tanaka, T., Suzuki, F., Ibaraki, K., and Takano T.
    • Journal Title

      Brain, Behavior, and Immunity

      Volume: 印刷中 Pages: 427-438

    • DOI

      10.1016/j.bbi.2019.04.023

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] “ヒト化ショウジョウバエ”の作出進む--非コード領域の変異の高感度アッセイ法の開発が課題2018

    • Author(s)
      高野敏行,茨木公英,大迫隆史
    • Journal Title

      生物の科学

      Volume: 72 Pages: 484-491

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Frequencies of chromosomal inversions in Drosophila melanogaster in Fukushima after the nuclear power plant accident.2018

    • Author(s)
      Itoh M, Kajihara R, Kato Y, Takano-Shimizu T, Inoue Y
    • Journal Title

      PLoS ONE

      Volume: 13 Issue: 2 Pages: e0192096-e0192096

    • DOI

      10.1371/journal.pone.0192096

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Selective breeding and selection mapping using a novel wild-derived heterogeneous stock of mice revealed two closely-linked loci for tameness.2017

    • Author(s)
      Matsumoto, Y., Goto, T., Nishino, J., Nakaoka, H., Tanave, A., Takano-Shimizu, T., Mott, R. F., and Koide, T.
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 4607-4607

    • DOI

      10.1038/s41598-017-04869-1

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Gain-of-function & loss-of-function mutations in disease candidate genes2019

    • Author(s)
      Takano, T.
    • Organizer
      2nd International Symposium for Model Organism Research on Human Rare Diseases
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] A large library of USA-human cDNA constructs and transgenic Drosophila stocks to facilitate translational research.2019

    • Author(s)
      S. Yamamoto, K.H. Wan, T. Johnson, H. K. Graves, V.H. Havana, H. Pan, D. Bei, O. Kania, S. Jankas, S. I. Park, W.W. Fisher, Y. Takashima, S. Ravani, M. Tomaru, T. Ohsako, M. F. Wangler, C. Warr, T. Takano-Shimizu, H.J. Bellen, & S.E. Celniker
    • Organizer
      60th Annual Drosophila Research Conference
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒト化ショウジョウバエでヒトゲノム配列の機能,比較解析はできるのか2018

    • Author(s)
      高野敏行
    • Organizer
      国立遺伝学研究所 研究集会「理論分子進化学の新機軸」
    • Related Report
      2018 Annual Research Report
  • [Presentation] 島田咲、村岡夕香、茨木公英、高野敏行、山口政光2018

    • Author(s)
      ショウジョウバエモデルを用いたヒト希少神経難病CMT原因遺伝子FIG4と遺伝学的に相互作用する遺伝子の同定
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ショウジョウバエ Rack1 は精子形成,受精の複数ステップで働く雄不妊遺伝子である2018

    • Author(s)
      茨木公英,中塚三保子,渡邉昌秀,白神真知,大迫隆史,都丸雅敏,高野敏行
    • Organizer
      日本遺伝学会第90回大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Tissue specificity of Enhancer activity of human ultra-conserved elements in fruit fly.2018

    • Author(s)
      T. Ohsako, T. Matsuda, D. Sasazaki, M. Tomaru, T. Awasaki, T. Takano
    • Organizer
      The 13th Japanese Drosophila Research Conference
    • Related Report
      2018 Annual Research Report
  • [Presentation] 先端昆虫モデル研究拠点ではじめる生物横断研究2018

    • Author(s)
      高野敏行
    • Organizer
      久留米大学医学部 Grand Round Seminar
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] ショウジョウバエで何ができる? 生物横断研究のハブとなる先端昆虫モデル研究拠点2018

    • Author(s)
      高野敏行
    • Organizer
      第1回 IRUD-Beyond モデル生物 国際シンポジウム モデル生物を用いた希少、未診断疾患へのアプローチ
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] ショウジョウバエ父性効果遺伝子の解析2018

    • Author(s)
      白神真知、中塚三保子、宮崎友、都丸雅敏、Tim Karr、高野敏行
    • Organizer
      2017年度生命科学系学会合同年次大会 第40回日本分子生物学会年会・第90回日本生化学会大会
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 精子形成が進化的に脆弱な要因再考2017

    • Author(s)
      高野敏行
    • Organizer
      国立遺伝学研究所 研究集会「ショウジョウバエの生殖システムと生殖戦略」
    • Place of Presentation
      三島,静岡
    • Year and Date
      2017-02-08
    • Related Report
      2016 Research-status Report
  • [Presentation] Enhancer activity of human ultra-conserved elements in fruit fly.2016

    • Author(s)
      T. Ohsako,R. Nakano, T. Matsuda, M. Tomaru, T. L. Karr, T. Takano
    • Organizer
      12th Japanese Drosophila Research Conference
    • Place of Presentation
      東京
    • Year and Date
      2016-09-09
    • Related Report
      2016 Research-status Report
  • [Presentation] Enhancer activity of vertebrate ultraconserved elements in fruit flies.2016

    • Author(s)
      T. Takano-Shimizu, T. Ohsako, T. Matsuda, M. Tomaru
    • Organizer
      The Allied Genetics Conference 2016
    • Place of Presentation
      Orland, Florida
    • Year and Date
      2016-07-13
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Book] Drosophila Models for Human Diseases2018

    • Author(s)
      M. Yamaguchi ed., 15 authors including Takano-Shimizu-Kouno, T.
    • Total Pages
      308
    • Publisher
      Springer
    • ISBN
      9789811305283
    • Related Report
      2018 Annual Research Report
  • [Book] バイオテクノロジーシリーズ ― AI導入によるバイオテクノロジーの発展 Development of Biotechnology by the Introduction of AI2018

    • Author(s)
      植田充美 監修/高野敏行他36名
    • Total Pages
      234
    • Publisher
      シーエムシー出版
    • ISBN
      4781313159
    • Related Report
      2017 Research-status Report

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

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