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A novel approach to the plasticity of region dependent regulation of DNA methylation

Research Project

Project/Area Number 15K14452
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Molecular biology
Research InstitutionKyushu University

Principal Investigator

Nakashima Kinichi  九州大学, 医学研究院, 教授 (80302892)

Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords神経科学 / エピジェネティクス / DNAメチル化
Outline of Final Research Achievements

In this research, we tried to establish a new approach to obtain the candidate proteins that control the target specificity of epigenetic modification enzymes by utilizing CRISPR/dCas9-based enChIP (engineered DNA-binding molecule-mediated chromatin immunoprecipitation). We found that dCas9 can bind to the target promoter region with high-specificity and without affecting DNA methylation status. However, binding of dCas9 significantly decreased the target gene expression, especially when binding region of dCas9 is located adjacent to the transcription start site. Our findings suggest that CRISPR/dCas9-based enChIP has limited utility in the adaptable regions but could be applied as an approach in other genomic regions.

Report

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

    (5 results)

All 2016 2015

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (3 results)

  • [Journal Article] Targeted DNA demethylation in vivo using dCas9-peptide repeat and scFv-TET1 catalytic domain fusions.2016

    • Author(s)
      Morita S, Noguchi H, Horii T, Nakabayashi K, Kimura M, Okamura K, Sakai A, Nakashima H, Hata K, Nakashima K, Hatada I
    • Journal Title

      Nat Biotechnol.

      Volume: 34 Issue: 10 Pages: 1060-1065

    • DOI

      10.1038/nbt.3658

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of DNMT1 in neural stem/precursor cells is critical for survival of newly generated neurons in the adult hippocampus2015

    • Author(s)
      Noguchi H, Kimura A, Murao N, Matsuda T, Namihira M, Nakashima K.
    • Journal Title

      Neurosci Res

      Volume: in press Pages: 1-11

    • DOI

      10.1016/j.neures.2015.01.014

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] ゲノム編集を利用したエピゲノムの書き換え2016

    • Author(s)
      森田純代, 野口浩史, 堀居拓郎, 中林一彦, 木村美香, 岡村浩司, 坂井 淳彦, 中嶋 秀行,秦健一郎, 中島欽一, ○畑田出穂
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] CRISPR/Casを用いたエピゲノム編集法2016

    • Author(s)
      森田純代, 野口浩史, 堀居拓郎, 中林一彦, 木村美香, 岡村浩司, 坂井 淳彦, 中嶋 秀行,秦健一郎, 中島欽一, ○畑田出穂
    • Organizer
      日本核酸医薬学会 第2回年会
    • Place of Presentation
      東京理科大学
    • Year and Date
      2016-11-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] Maintenance DNA methyltransferase DNMT1 contributes to the fate regulation of neural stem cells through DNA methylation-dependent and-independent manners during cortical development2015

    • Author(s)
      野口浩史、波平昌一、佐野坂司、辻村啓太、深尾陽一朗、五十嵐勝秀、木村文香、中嶋秀行、中島欽一
    • Organizer
      第40回内藤コンファレンス
    • Place of Presentation
      シャトレーゼガトーキングダムサッポロ、札幌市
    • Year and Date
      2015-09-15
    • Related Report
      2015 Research-status Report

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

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