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Development of visible detection system for epimutation

Research Project

Project/Area Number 15K00561
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Risk sciences of radiation and chemicals
Research InstitutionNational Institute of Health Sciences

Principal Investigator

Sugiyama Kei-ichi  国立医薬品食品衛生研究所, 変異遺伝部, 室長 (80356237)

Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
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)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsエピジェネティック毒性 / 酵母 / 凝集 / FLO1 / エピジェネティクス / DNAメチル化酵素 / FLO1遺伝子 / エピ変異原 / ヒストン修飾
Outline of Final Research Achievements

With regard to epigenetic mutation that are considered to be involved in diseases such as carcinogenesis, there is no validated detection system for epigenetic mutation. In this study, we attempted to construct a bioassay system that can easily detect epigenetic mutation with a microorganism. Budding yeast is an eukaryotic single-celled microorganism. It has been found that the yeasts transformed with cDNAs of human DNA methyltransferase genes apparently show a flocculation phenotype. Therefore, we tried to construct an epigenetic mutation detection system based on a reporter assay using the FLO1 flocculation gene. In this study, our findings suggest that yeast flocculation is a useful marker for the detection of epigenetic mutation.

Academic Significance and Societal Importance of the Research Achievements

発がんの予測に有効な遺伝毒性試験の結果をより精緻化できる潜在能力を有すると期待されるエピジェネティック毒性試験系について、そのプロトタイプを独自の着想に基づき構築しかつその有効性を認めた点は、今後の化学物質による発がん性評価を考える上で新たな視座を与える可能性がある。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (16 results)

All 2019 2018 2017 2016 2015

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Acknowledgement Compliant: 1 results) Presentation (12 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Inhibitory effect of ochratoxin A on DNMT-mediated flocculation of yeast2019

    • Author(s)
      Kei-ichi Sugiyama, Hiroko Furusawa, Petr Gruz, Mawo Kinoshita, Masamitsu Honma
    • Journal Title

      Mutagenesis

      Volume: 印刷中

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Detection of epigenetic mutagens including anthracene-derived compounds using yeast FLO1 promoter GFP reporter gene assay2017

    • Author(s)
      Sugiyama Kei-ichi、Furusawa Hiroko、Gruz Petr、Honma Masamitsu
    • Journal Title

      Mutagenesis

      Volume: 32 Issue: 4 Pages: 429-435

    • DOI

      10.1093/mutage/gex009

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Functional role of DNA methylation at the FLO1 promoter in budding yeast2017

    • Author(s)
      Sugiyama Kei-ichi、Furusawa Hiroko、Gruz Petr、Honma Masamitsu
    • Journal Title

      FEMS Microbiology Letters

      Volume: 364 Issue: 22 Pages: 1-8

    • DOI

      10.1093/femsle/fnx221

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Epigenetic mutagen as histone modulator can be detected by yeast flocculation2016

    • Author(s)
      Sugiyama, K., Furusawa, H., Shimizu, M., Gruz, P. and Honma, M
    • Journal Title

      Mutagenesis

      Volume: 31 Issue: 6 Pages: 687-693

    • DOI

      10.1093/mutage/gew041

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 酵母凝集遺伝子FLO1プロモーター活性を指標としたDNMT阻害様活性の検出2018

    • Author(s)
      杉山圭一、古沢博子、グルーズ ピーター、本間正充
    • Organizer
      第12回日本エピジェネティクス研究会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] DNAメチル化が出芽酵母のFLO1プロモーター活性に及ぼす影響2018

    • Author(s)
      杉山圭一、古沢博子、グルーズ ピーター、本間正充
    • Organizer
      酵母遺伝学フォーラム第51回研究報告会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ヒトDNMT酵母による環境中からのエピジェネティック変異原様活性の検出2018

    • Author(s)
      杉山圭一、古沢博子、木下麻緖、グルーズ ピーター、本間正充
    • Organizer
      日本環境変異原学会第47回大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 酵母凝集反応を利用した新規エピジェネティック変異原検出法の開発2017

    • Author(s)
      杉山圭一、古沢博子、グルーズ ピーター、本間正充
    • Organizer
      日本農芸化学会2017年度大会
    • Place of Presentation
      京都
    • Year and Date
      2017-03-19
    • Related Report
      2016 Research-status Report
  • [Presentation] 酵母凝集反応を指標としたエピ変異原スクリーニング系の開発2017

    • Author(s)
      杉山圭一、古沢博子、グルーズ ピーター、本間正充
    • Organizer
      第11回日本エピジェネティクス研究会年会
    • Related Report
      2017 Research-status Report
  • [Presentation] 出芽酵母の凝集関連遺伝子FLO1プロモーターにおけるDNAメチル化の影響2017

    • Author(s)
      杉山圭一、古沢博子、グルーズ ピーター、本間正充
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Effect of epigenetic modifiers on the flocculation of human DNMT gene-transformed yeasts2016

    • Author(s)
      Sugiyama, K., Furusawa, H. and Honma, M
    • Organizer
      14th International Congress on Yeasts (2016)
    • Place of Presentation
      Awaji, Japan
    • Year and Date
      2016-09-12
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 酵母凝集反応をエンドポイントとしたエピ変異原検出系2016

    • Author(s)
      杉山圭一、古沢博子、清水雅富、グルーズ ピーター、本間正充
    • Organizer
      酵母遺伝学フォーラム第49回研究報告会
    • Place of Presentation
      神戸
    • Year and Date
      2016-09-10
    • Related Report
      2016 Research-status Report
  • [Presentation] 酵母凝集反応を利用した新規なエピ変異原可視化検出系の開発2016

    • Author(s)
      杉山圭一、古沢博子、清水雅富、本間正充
    • Organizer
      日本農芸化学会大会
    • Place of Presentation
      札幌
    • Year and Date
      2016-03-30
    • Related Report
      2015 Research-status Report
  • [Presentation] Epigenetic modifiers are visibly detectable by human DNMTs transgenic yeast2016

    • Author(s)
      Sugiyama, K., Furusawa, H. and Honma, M
    • Organizer
      International Symposium for RIKEN Epigenetics Program 2016
    • Place of Presentation
      和光
    • Year and Date
      2016-02-15
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] In vivo DNAメチル化酵素阻害可視化システムの開発2015

    • Author(s)
      杉山圭一、古沢博子、本間正充
    • Organizer
      日本生化学会大会
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-02
    • Related Report
      2015 Research-status Report
  • [Presentation] 酵母をプラットフォームとしたエピジェネティック変異原検出系構築の試み2015

    • Author(s)
      杉山圭一、古沢博子、本間正充
    • Organizer
      日本環境変異原学会
    • Place of Presentation
      福岡
    • Year and Date
      2015-11-27
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2020-03-30  

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