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Establishment of drug screening system for mental disorder by generation of novel epigenome editing proteins

Research Project

Project/Area Number 15K21661
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Neurophysiology / General neuroscience
Medical genome science
Research InstitutionNational Institute of Advanced Industrial Science and Technology

Principal Investigator

Hirano Kazumi  国立研究開発法人産業技術総合研究所, バイオメディカル研究部門, 研究員 (40707709)

Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords精神疾患 / エピジェネティクス / DNAメチル化 / エピゲノム編集 / DNMT / LSD1 / 神経幹細胞 / ジンクフィンガー / 疾患モデル細胞 / メチル化
Outline of Final Research Achievements

Recently, the relationship between mental disorder and abnormal DNA methylation in neuron has been reported. However, this detail mechanism remains unknown. To address this issue, we generated novel epigenome editing system using zinc finger protein (ZF) and DNA methyltransferase (DNMT). This system, named ZF-DNMT, induced DNA methylation on target genome region and reduced the expression level of target gene in human neural stem cells. Furthermore, we focused on histone demethylase LSD1, which is used for epigenome editing and interacts DNMT, and found that LSD1 is necessary for human neurogenesis.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (7 results)

All 2017 2016 2015 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (4 results) (of which Int'l Joint Research: 2 results) Remarks (1 results)

  • [Journal Article] New insight into LSD1 function in human cortical neurogenesis.2016

    • Author(s)
      Hirano K, Namihira M.
    • Journal Title

      Neurogenesis

      Volume: 3 Issue: 1 Pages: e1249195-e1249195

    • DOI

      10.1080/23262133.2016.1249195

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] LSD1 Mediates Neuronal Differentiation of Human Fetal Neural Stem Cells by Controlling the Expression of a Novel Target Gene, HEYL.2016

    • Author(s)
      Hirano K, Namihira M.
    • Journal Title

      Stem Cells

      Volume: 34 Issue: 7 Pages: 1-11

    • DOI

      10.1002/stem.2362

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Lysine-Specific Demethylase 1 (LSD1) and its downstream target gene HEYL are important for neurogenesis of human fetal neural stem cells2017

    • Author(s)
      Kazumi Hirano, Masakazu Namihira
    • Organizer
      KEYSTONE SYMPOSIA (J2)
    • Place of Presentation
      Resort at Squaw Creek, California, USA
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒストン脱メチル化酵素LSD1はヒト神経幹細胞のニューロン分化を制御する2016

    • Author(s)
      平野和己、波平昌一
    • Organizer
      第10回日本エピジェネティクス研究会年会
    • Place of Presentation
      千里ライフサイエンスセンター(大阪)
    • Year and Date
      2016-05-19
    • Related Report
      2016 Annual Research Report
  • [Presentation] Histone demethylase LSD1 controls Notch signaling and GABAergic neuronal differentiation in human neural stem cell2015

    • Author(s)
      Kazumi Hirano, Masakazu Namihira
    • Organizer
      Society for Neuroscience Neuroscience 2015
    • Place of Presentation
      Chicago, USA
    • Year and Date
      2015-10-18
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] LSD1はヒト神経幹細胞のGABA作動性ニューロンへの分化を制御する2015

    • Author(s)
      平野和己、波平昌一
    • Organizer
      第9回日本エピジェネティクス研究会年会
    • Place of Presentation
      東京/学術総合センター 一橋講堂
    • Year and Date
      2015-05-26
    • Related Report
      2015 Research-status Report
  • [Remarks] ヒトの神経細胞の発生を調節するタンパク質の機能を発見

    • URL

      http://www.aist.go.jp/aist_j/press_release/pr2016/pr20160328/pr20160328.html

    • Related Report
      2016 Annual Research Report

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Published: 2015-04-16   Modified: 2018-03-22  

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