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Functional analysis epigenetics regulators in carcinogenesis

Research Project

Project/Area Number 18590066
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionNagoya City University

Principal Investigator

OSADA Shigehiro  Nagoya City University, Graduate School of Pharmaceutical Sciences, Department of Molecular Biology, Associate Professor (40263305)

Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥4,040,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥540,000)
Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywordschromatin / histone / epignetics / acetylation / histone variant / gene expression / carcinogenesis / tumor marker / 脱アセチル化 / ヒストン修飾 / 化学発がん / 前がん病変
Research Abstract

Great effort has been directed towards understanding the mechanism of malignant transformation derived from genetic mutations. Nowadays, studies on epigenetic mutations in cancer are also required. In this project, we focused on epigenetics modulators (histone modification enzymes and histone variants), up-regulated during chemically induced hepatocarcinogenesis.
1. Effect of over expression of histone modification enzymes on the malignant transformation.
We identified histone modification enzymes, which induced during hepatocarcinogenesis by RT-PCR, DNA microarray, and Western blot analyses. One of them, histone acetyltransferase, regulated the transformation activity mediated by mutated ras oncogene. Histone deacetylase, one of other modulators, promoted anchorage independent growth in soft agarose.
2. Effect of over expression of histone modification enzymes on expression of the tumor marker gene.
Glutathione transferase placental form (GST-P) is specifically dramatically induced during … More hepatocarcinogenesis and recognized as a reliable tumor marker. Transcriptional factor Nrf2/MafK heterodimer is one of the most important positive regulators on GST-P expression during hepatocarcinogenesis. We revealed that one of histone acetyltransferase, which was over-expressed in nuclear extracts from livers including hyperplastic nodules, acted as a cofactor of Nrf2/MafK heterodimer and induced expression of GST-P.
3. Functional analysis of the histone variant in yeast.
We found that H2A.Z, one of histone variants, was induced during hepatocarcinogenesis. Tb gain insights of molecular function of H2A.Z, we generated a H2A.Z deletion strain in Saccharomyces cerevisiae. The H2A.Z deletion strain was sensitive to genotoxic reagents. Further, we observed the sensitivity to nickel compounds, which decrease acetylation levels of all four histones and increase ubiquitylation of H2A and H2B and dimethylation of H3 lysine 9, and revealed that the nickel toxicity appeared with the incorporation of H2AZ into chromatin mediated by the chromatin remodeling factor, but not acetylation of H2AZ. Less

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (23 results)

All 2008 2007 2006

All Journal Article (11 results) (of which Peer Reviewed: 4 results) Presentation (12 results)

  • [Journal Article] FAD24,a regulator of adipogenesis and DNA replication,inhibits H-RAS-mediated transformation by repressing NF-k B activity2008

    • Author(s)
      Yoshikazu Johmura
    • Journal Title

      Biochem.Biophys.Res.Commun 369

      Pages: 464-470

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] FAD24, a regulator of adipogenesis and DNA replication, inhibits H-RAS-mediated transformation by repressing NF-KB activity2008

    • Author(s)
      Yoshikazu, Johmura
    • Journal Title

      Biochem. Biophys. Res. Commun 369

      Pages: 464-470

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] FAD24, a regulator of adipogenesis and DNA replication, inhibits H-RAS-mediated transformation by repressing NF-κB activity.2008

    • Author(s)
      Johmura, Y.
    • Journal Title

      Biochem. Biophys. Res. Commun. 369

      Pages: 464-470

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Histone acetyltransferase MOZ is induced during hepatocarcinogenesis,acts as a coactivator of Nrf2/MafK and induces tumor marker gene expression2007

    • Author(s)
      Kumiko Ohta
    • Journal Title

      Biochemical Journal 402

      Pages: 559-566

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Histone acetyltransferase MOZ is induced during hepatocarcinogenesis, acts as a coactivator of Nrf2/MafK and induces tumor marker gene expression2007

    • Author(s)
      Kumiko, Ohta
    • Journal Title

      Biochemical Journal 402

      Pages: 559-566

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Histone modification enzymes induced during chemical hepatocarcinogenesis2007

    • Author(s)
      Shigehiro, Osada
    • Journal Title

      Yakugaku Zasshi 127

      Pages: 469-479

    • NAID

      110006240156

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Histone acetyltransferase MOZ is induced during hepatocarcinogenesis, acts as a coactivator of Nrf2/MafK and induces tumor marker gene expression.2007

    • Author(s)
      Kumiko Ohta
    • Journal Title

      Biochemical Journal 402・3

      Pages: 559-566

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Histone modification enzymes induced during chemical hepatocarcinogenesis.2007

    • Author(s)
      Shigehiro Osada
    • Journal Title

      Yakugaku Zasshi 127・3

      Pages: 469-479

    • NAID

      110006240156

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Altered gene expression of transcriptional regulatory factors in tumor marker-positive cells during chemically induced hepatocarcinogenes2006

    • Author(s)
      Shigehiro Osada
    • Journal Title

      Toxicology Letters 167

      Pages: 106-113

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Altered gene expression of transcriptional regulatory factors in tumor marker-positive cells during chemically induced hepatocarcinogenes2006

    • Author(s)
      Shigehiro, Osada
    • Journal Title

      Toxicology Letters 167

      Pages: 106-113

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Altered gene expression of transcriptional regulatory factors in tumor marker-positive cells during chemically induced hepatocarcinogenes2006

    • Author(s)
      Shigehiro Osada
    • Journal Title

      Toxicology letters 167・2

      Pages: 106-113

    • Related Report
      2006 Annual Research Report
  • [Presentation] 発がん初期に発現変化するクロマチン関連因子による転写制御2008

    • Author(s)
      長田 茂宏
    • Organizer
      第128年会日本薬学会
    • Place of Presentation
      横浜
    • Year and Date
      2008-03-26
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Transcriptional regulation by epigenetics modulators induced during hepatocarcinogenesis2008

    • Author(s)
      Shigehiro, Osada
    • Organizer
      The 128th Annual Meeting of the Pharmaceutical Society of Japan
    • Place of Presentation
      Yokohama
    • Year and Date
      2008-03-26
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 発がん初期に発現変化するクロマチン関連因子による転写制御2008

    • Author(s)
      長田 茂宏
    • Organizer
      第128年会 日本薬学会
    • Place of Presentation
      横浜
    • Year and Date
      2008-03-26
    • Related Report
      2007 Annual Research Report
  • [Presentation] Characterization of HAC9 induced during hepatocarcinogenesis in rat2007

    • Author(s)
      Takayuki, Yura
    • Organizer
      BMB 2007, Biochemistry and Molecular Biology Joint Meeting
    • Place of Presentation
      Yokohama
    • Year and Date
      2007-12-14
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ラット肝化学発がん過程において発現上昇するHdac9の解析2007

    • Author(s)
      由良 隆行
    • Organizer
      第30回日本分子生物学会年会、第80回日本生化学会大会合同大会
    • Place of Presentation
      横浜
    • Year and Date
      2007-12-14
    • Related Report
      2007 Annual Research Report
  • [Presentation] Mechanism of adipocyte differentiation regulated by a novel gene fad24 which is involved in DNA replication2007

    • Author(s)
      Yoshikazu, Johmura
    • Organizer
      BMB 2007, Biochemistry and Molecular Biology Joint Meeting
    • Place of Presentation
      Yokohama
    • Year and Date
      2007-12-12
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Functional analysis of novel gene fad24, regulator of adipogenesis, in malignant transformation2007

    • Author(s)
      Masanori, Suzuki
    • Organizer
      The 53th Annual Meeting of the Pharmaceutical Society of Japan Tokai Branch
    • Place of Presentation
      Nagoya
    • Year and Date
      2007-07-07
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 脂肪細胞分化を制御する新規遺伝子fad24の細胞の癌化における機能解析2007

    • Author(s)
      鈴木正憲
    • Organizer
      第53回 日本薬学会東海支部大会
    • Place of Presentation
      名古屋
    • Year and Date
      2007-07-07
    • Related Report
      2007 Annual Research Report
  • [Presentation] Functional analysis of histone variant H2A.Z in nickel sencitivity2007

    • Author(s)
      Urara, Gomita
    • Organizer
      The 71th Annual Meeting of the Japanese Biochemical Society, Chubu Branch
    • Place of Presentation
      Nagoya
    • Year and Date
      2007-05-19
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ニッケル感受性を利用したヒストンバリアントH2A. Zの機能解析2007

    • Author(s)
      五味田 麗
    • Organizer
      第71回 日本生化学会中部支部例会
    • Place of Presentation
      名古屋
    • Year and Date
      2007-05-19
    • Related Report
      2007 Annual Research Report
  • [Presentation] Characterization of chromatin assembly factor ASF1 that interacts with histone acetyltransferase complex2007

    • Author(s)
      Shigehiro, Osada
    • Organizer
      The 127th Annual Meeting of the Pharmaceutical Society of Japan
    • Place of Presentation
      Toyama
    • Year and Date
      2007-03-29
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Identification of chromatin assembly factor Asflp-associated factors2006

    • Author(s)
      Shigehiro, Osada
    • Organizer
      20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress
    • Place of Presentation
      Kyoto
    • Year and Date
      2006-06-23
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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