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Research on epigenetic regulation of aging and cancer by CHD8/histone H1 complex

Research Project

Project/Area Number 22680061
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Carcinogenesis
Research InstitutionKyushu University

Principal Investigator

NISHIYAMA Masaaki  九州大学, 生体防御医学研究所, 助教 (50423562)

Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥25,610,000 (Direct Cost: ¥19,700,000、Indirect Cost: ¥5,910,000)
Fiscal Year 2011: ¥12,090,000 (Direct Cost: ¥9,300,000、Indirect Cost: ¥2,790,000)
Fiscal Year 2010: ¥13,520,000 (Direct Cost: ¥10,400,000、Indirect Cost: ¥3,120,000)
Keywords遺伝子 / 発生・分化 / 動物 / 癌 / 老化 / 生物
Research Abstract

We recently have found that a chromatin remodeling factor CHD8 suppresses p53 function by recruiting the linker histone H1 on chromatin, and expected that a CHD8/histone H1 complex may play an important role in chromatin remodeling in cellular senescence. First, we investigated the effect of CHD8 overexpression on cellular senescence in normal cells, and revealed that forced expression of CHD8 inhibits p53-induced cellular senescence. We next generated CHD8-inducible transgenic mice, and revealed that CHD8 has a potent transformating activity. In normal aging or premature aging mice, we found that the expression level of CHD8/histone H1 is markedly decreased. Furthermore, we found that cellular senescence is induced in histone H1-knockdown cells or the cells derived from CHD8-knockout mice. Taken together, it is expected that CHD8 not only has anti-aging effect, but also functions as an oncogene.

Report

(3 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • Research Products

    (26 results)

All 2012 2011 2010 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (13 results) Book (4 results) Remarks (3 results)

  • [Journal Article] Histone H1 recruitment by CHD8 is essential for suppression of the Wnt-beta-catenin signaling pathway2012

    • Author(s)
      Nishiyama M., Skoultchi AI., Nakayama KI.
    • Journal Title

      Mol. Cell. Biol

      Volume: 32 Pages: 501-12

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Histone H1 recruitment by CHD8 is essential for suppression of the Wnt-β-catenin signaling pathway2012

    • Author(s)
      Nishiyama M, Skoultchi AI, Nakayama KI
    • Journal Title

      Molecular and Cellular Biology

      Volume: 32 Issue: 2 Pages: 501-512

    • DOI

      10.1128/mcb.06409-11

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of CHD7s as a novel splicing variant of CHD7 with functions similar and antagonistic to those of the full-length CHD7_L2012

    • Author(s)
      Kita Y, Nishiyama M, Nakayama KI
    • Journal Title

      Genes to Cells

      Volume: (in press)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The FBXL5-IRP2 axis is integral to control of iron metabolism in vivo2011

    • Author(s)
      Moroishi T., Nishiyama M., Takeda Y., Iwai K., Nakayama KI.
    • Journal Title

      Cell Metab

      Volume: 14 Pages: 339-51

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] The FBXL5-IRP2 axis is integral to control of iron metabolism in vivo2011

    • Author(s)
      Moroishi T., Nishiyama M., Takeda Y., Iwai K., Nakayama KI.
    • Journal Title

      Cell Metabolism

      Volume: 14 Issue: 3 Pages: 339-351

    • DOI

      10.1016/j.cmet.2011.07.011

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of CHD7S as a novel splicing variant of CHD7 with functions similar and antagonistic to those of the full-length CHD7L

    • Author(s)
      Kita Y., Nishiyama M., Nakayama KI.
    • Journal Title

      Genes Cells

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Presentation] CHD8によるヒストンH1のリクルートはWnt/β-カテニンシグナル伝達の抑制に必須である2011

    • Author(s)
      西山正章,中山敬一
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2011-12-13
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] ユビキチン化による鉄代謝制御機構2011

    • Author(s)
      諸石寿朗,西山正章,武田有紀子,岩井一宏,中山敬一
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2011-12-13
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] クロマチンリモデリング因子CHD8のL型アイソフォームはマウスの個体発生や細胞分化に必須である2011

    • Author(s)
      片山雄太,西山正章,中山敬一
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2011-12-13
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] ユビキチン化による鉄代謝制御機構2011

    • Author(s)
      諸石寿朗,西山正章,武田有紀子,岩井一宏,中山敬一
    • Organizer
      第35回日本鉄バイオサイエンス学会学術集会
    • Place of Presentation
      徳島
    • Year and Date
      2011-09-10
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] Loss of Fbxl5 results in deregulation of iron metabolism in mice2011

    • Author(s)
      Toshiro Moroishi, Masaaki Nishiyama, Kanae Yumimoto, Masaki Matsumoto, Kazuhiro Iwai, Keiichi Nakayama
    • Organizer
      6th Cold Spring Harbor meeting on The Ubiquitin Family
    • Place of Presentation
      Cold Spring Harbor, U. S. A
    • Year and Date
      2011-05-17
    • Related Report
      2011 Final Research Report
  • [Presentation] Loss of SCFFbxl5 results in deregulation of iron metabolism in mice2011

    • Author(s)
      Toshiro Moroishi, Masaaki Nishiyama, Kanae Yumimoto, Masaki Matsumoto, Kazuhiro Iwai, Keiichi Nakayama
    • Organizer
      The Joint Symposium of the 7th Global-COE International Symposiumand 6th Young Investigators Forum
    • Place of Presentation
      Bintan island, Indonesia
    • Year and Date
      2011-02-10
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] Loss of Fbx15 results in deregulation of iron metabolism in mice2011

    • Author(s)
      Toshiro Moroishi, Masaaki Nishiyama, Kanae Yumimoto, Masaki Matsumoto, Kazuhiro Iwai, Keiichi I.Nakayama
    • Organizer
      6th Cold Spring Harbor meeting on The Ubiquitin Family
    • Place of Presentation
      Cold Spring Harbor, U.S.A.
    • Related Report
      2011 Annual Research Report
  • [Presentation] クロマチンリモデリング因子CHD8のL型アイソフォームはマウスの個体発生や細胞分化に必須である2010

    • Author(s)
      片山雄太,西山正章,中山敬一
    • Organizer
      Biochemistry and Molecular Biology 2010
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-08
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] 発生過程におけるアポトーシスの新しい制御機構2010

    • Author(s)
      西山正章,中山敬一
    • Organizer
      クロマチンリモデリングによるp53のエピジェネティックコントロールBiochemistry and Molecular Biology 2010
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-07
    • Related Report
      2011 Final Research Report
  • [Presentation] ディファレンシャル・プロテオミクス技術を用いた鉄代謝制御ユビキチンリガーゼFbxl5の網羅的基質探索と個体における機能解析2010

    • Author(s)
      諸石寿朗,西山正章,岩井一宏,中山敬一
    • Organizer
      Biochemistry and Molecular Biology 2010
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-07
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] 発生過程におけるアポトーシスの新しい制御機構:クロマチンリモデリングによるp53のエピジェネティックコントロール2010

    • Author(s)
      西山正章, 中山敬一
    • Organizer
      Biochemistry and Molecular Biology 2010
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-07
    • Related Report
      2010 Annual Research Report
  • [Presentation] ディファレンシャル・プロテオミクス技術を用いた鉄代謝制御ユビキチンリガーゼFbxl5の機能解析CREST2010

    • Author(s)
      諸石寿朗,西山正章,岩井一宏,中山敬一
    • Organizer
      生命システムの動作原理と基盤技術
    • Place of Presentation
      研究領域
    • Year and Date
      2010-06-01
    • Related Report
      2011 Final Research Report
  • [Presentation] ディファレンシャル・プロテオミクス技術を用いた鉄代謝制御ユビキチンリガーゼFbxl5の機能解析2010

    • Author(s)
      諸石寿朗, 西山正章, 岩井一宏, 中山敬一
    • Organizer
      CREST「生命システムの動作原理と基盤技術」研究領域平成22年度公開シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2010-06-01
    • Related Report
      2010 Annual Research Report
  • [Book] 初期発生におけるCHD8依存的なp53の制御機構2011

    • Author(s)
      喜多泰之, 西山正章, 中山敬一
    • Publisher
      BIO Clinica
    • Related Report
      2011 Final Research Report
  • [Book] BIO Clinica2011

    • Author(s)
      喜多泰之, 西山正章, 中山敬
    • Total Pages
      5
    • Publisher
      北隆館
    • Related Report
      2011 Annual Research Report
  • [Book] 発生過程におけるアポトーシスの新しい制御機構:クロマチンリモデリングによるp53のエピジェネティックコントロール実験医学増刊272010

    • Author(s)
      西山正章, 中山敬一
    • Related Report
      2011 Final Research Report
  • [Book] 実験医学増刊2010

    • Author(s)
      西山正章, 中山敬一
    • Total Pages
      7
    • Publisher
      羊土社
    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.bioreg.kyushu-u.ac.jp/saibou/index.html

    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://www.bioreg.kyushu-u.ac.jp/saibou/index.html

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.bioreg.kyushu-u.ac.jp/saibou/index.html

    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2016-04-21  

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