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Elucidation of the mechanism of nucleosomal structural change mediated by histone modifications

Research Project

Project/Area Number 21370052
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional biochemistry
Research InstitutionThe University of Tokyo

Principal Investigator

HORIKOSHI Masami  東京大学, 分子細胞生物学研究所, 准教授 (70242089)

Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Fiscal Year 2011: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2009: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Keywords遺伝子の情報発現と複製 / 遺伝子 / 酵素 / 生体分子 / 構造変換 / 蛋白質 / 発現制御
Research Abstract

Nucleosomes around the promoter region are disassembled for transcription in response to various signals, such as acetylation and methylation of histones. Although the interactions between histone-acetylation- recognizing bromodomains and factors involved in nucleosome disassembly have been reported, no structural basis connecting histone modifications and nucleosome disassembly has been obtained. We determined at 3.3 A resolution the crystal structure of histone chaperone cell cycle gene 1 (CCG1) interacting factor A/antisilencing function 1 (CIA/ASF1) in complex with the double bromodomain in the CCG1/TAF1/TAF(II)250 subunit of transcription factor IID. Structural, biochemical, and biological studies suggested that interaction between double bromodomain and CIA/ASF1 is required for their colocalization, histone eviction, and pol II entry at active promoter regions. Furthermore, the present crystal structure has characteristics that can connect histone acetylation and CIA/ASF1-mediated histone eviction. These findings suggest that the molecular complex between CIA/ASF1 and the double bromodomain plays a key role in site-specific histone eviction at active promoter regions. The model we propose in this study is the initial structure-based model of the biological signaling fromhistone modifications to structural change of the nucleosome (hi-MOST model).

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (33 results)

All 2012 2011 2010 2009 Other

All Journal Article (13 results) (of which Peer Reviewed: 13 results) Presentation (17 results) (of which Invited: 1 results) Book (2 results) Remarks (1 results)

  • [Journal Article] Nucleosome surface containing nucleosomal DNA entry/exit site regulates H3-K36me3 via DNA entry/exit site regulates H3-K36me3 via2012

    • Author(s)
      H.Endo, Y.Nakabayashi, S.Kawashima, T.Enomoto, M.Seki & M.Horikoshi
    • Journal Title

      Genes Cells

      Volume: 17 Issue: 1 Pages: 65-81

    • DOI

      10.1111/j.1365-2443.2011.01573.x

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Global analysis for functional residues of histone variant Htz1 using the comprehensive point mutant library2011

    • Author(s)
      A.Kawano, Y.Hayashi, S.Noguchi, H.Handa, M.Horikoshi & Y.Yamaguchi
    • Journal Title

      Genes Cells

      Volume: 16 Issue: 5 Pages: 590-607

    • DOI

      10.1111/j.1365-2443.2011.01512.x

    • Related Report
      2011 Annual Research Report 2011 Final Research Report 2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Biphasic chromatin binding of histone chaperone FACT during eukaryotic chromatin DNA replication2011

    • Author(s)
      L.R.Kundu, M.Seki, H.Murofushi,A.Furukohri, S.Waga, A.J.Score, J.J.Blow, M.Horikoshi, T.Enomoto & S.Tada
    • Journal Title

      Biochim.Biophys.Acta

      Volume: 1813 Issue: 6 Pages: 1129-36

    • DOI

      10.1016/j.bbamcr.2011.01.002

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Global analysis of core histones reveals nucleosomal surfaces required for chromosomebi-orientation2011

    • Author(s)
      S.Kawashima, Y.Nakabayashi, K.Matsubara, N.Sano, T.Enomoto, K.Tanaka, M.Seki & M.Horikoshi
    • Journal Title

      EMBO J.

      Volume: 30 Issue: 16 Pages: 3353-3367

    • DOI

      10.1038/emboj.2011.241

    • Related Report
      2011 Annual Research Report 2011 Final Research Report 2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The histone chaperone FACT maintains replication fork rates2011

    • Author(s)
      T.Abe, K.Sugimura, Y.Hosono, Y.Takami, M.Akita, A.Yoshimura, S.Tada, T.Nakayama, H.Murofushi, K.Okumura, S.Takeda, M.Horikoshi, M.Seki & T.Enomoto
    • Journal Title

      J.Biol.Chem.

      Volume: 286 Issue: 35 Pages: 30504-30512

    • DOI

      10.1074/jbc.m111.264721

    • Related Report
      2011 Annual Research Report 2011 Final Research Report 2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The roles of histone chaperone CIA/Asf1 in nascent DNA elongation during nucleosome replication.2011

    • Author(s)
      K.Ishikawa, T.Ohsumi, S.Tada, R.Natsume, L.R.Kundu, N.Nozaki, T.Senda, T.Enomoto, M.Horikoshi & M.Seki
    • Journal Title

      Genes Cells

      Volume: 16 Issue: 10 Pages: 1050-1062

    • DOI

      10.1111/j.1365-2443.2011.01549.x

    • Related Report
      2011 Annual Research Report 2011 Final Research Report 2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Biphasic chromatin binding of histone chaperone FACT during eukaryotic chromatin DNA replication2011

    • Author(s)
      L.Kundu, et al
    • Journal Title

      Biochim.Biophys.Acta

      Volume: 1813 Pages: 1129-1136

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structure of the histone chaperone CIA/ASF1-double bromodomain complex connecting histone modifications and site-specific histone eviction2010

    • Author(s)
      Y.Akai, N.Adachi, Y.Hayashi, M.Eitoku, N.Sano, R.Natsume, N.Kudo, M.Tanokura, T.Senda & M.Horikoshi
    • Journal Title

      Proc.Natl.Acad.Sci.U.S.A.

      Volume: 107 Issue: 18 Pages: 8153-8158

    • DOI

      10.1073/pnas.0912509107

    • Related Report
      2011 Final Research Report 2010 Annual Research Report 2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Global analysis of functional relationships between histone point mutations and the effects of histone deacetylase inhibitors2010

    • Author(s)
      L.Sato, S.Noguchi, Y.Hayashi, M.Sakamoto & M.Horikoshi
    • Journal Title

      Genes Cells

      Volume: 15 Issue: 6 Pages: 553-594

    • DOI

      10.1111/j.1365-2443.2010.01408.x

    • Related Report
      2011 Final Research Report 2010 Annual Research Report 2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chromatin dynamics mediated by histone modifiers and histone chaperones in postreplicative recombination2010

    • Author(s)
      H.Endo, S.Kawashima, L.Sato, M.S.Lai, T.Enomoto, M.Seki & M.Horikoshi
    • Journal Title

      Genes Cells

      Volume: 15 Issue: 9 Pages: 945-958

    • DOI

      10.1111/j.1365-2443.2010.01435.x

    • Related Report
      2011 Final Research Report 2010 Annual Research Report 2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Theoretical framework for the histone modification network: modifications in the unstructured histone tails form a robust scale-free network2009

    • Author(s)
      Y.Hayashi, T.Senda, N.Sano & M.Horikoshi
    • Journal Title

      Genes Cells

      Volume: 14 Issue: 7 Pages: 789-806

    • DOI

      10.1111/j.1365-2443.2009.01314.x

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Global analysis of mutual interaction surfaces of nucleosomes with comprehensive point mutants2009

    • Author(s)
      M.Sakamoto, S.Noguchi, S.Kawashima, Y.Okada, T.Enomoto, M.Seki & M.Horikoshi
    • Journal Title

      Genes Cells

      Volume: 14 Issue: 11 Pages: 1271-1330

    • DOI

      10.1111/j.1365-2443.2009.01350.x

    • Related Report
      2011 Final Research Report 2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Theoretical framework for the histone modification network : modifications in the unstructured histone tails form a robust scale-free network2009

    • Author(s)
      Y.Hayashi, et al.
    • Journal Title

      Genes Cells

      Volume: 14 Pages: 789-806

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] Studies on chromatin regulation by utilizing histone-GLibrary2012

    • Author(s)
      M.Horikoshi
    • Organizer
      Keystone Symposia-Chromatin Dynamics
    • Place of Presentation
      Keystone (Colorado), USA
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] Theoretical framework for the histone modification networks2012

    • Author(s)
      M.Horikoshi
    • Organizer
      Cold Spring Harbor Laboratory Meeting-Systems Biology: Global Regulation of Gene Expression
    • Place of Presentation
      Cold Spring Harbor (New York), USA
    • Related Report
      2011 Final Research Report
  • [Presentation] Theoretical framework for the histone modification networks2012

    • Author(s)
      M.Horikoshi
    • Organizer
      Cold Spring Harbor Laboratory Meeting- Systems Biology: Global Regulation of Gene Expression 2012
    • Place of Presentation
      Cold Spring Harbor (New York), USA
    • Related Report
      2011 Annual Research Report
  • [Presentation] 生化学を基軸に独創性、そして独走性を目指した30年に及ぶ遺伝子制御研究2011

    • Author(s)
      堀越正美
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      京都市
    • Year and Date
      2011-09-23
    • Related Report
      2011 Final Research Report
  • [Presentation] Network-Based Histone "Modification Web" Theory and "DESS" Strategy for Elucidating the Physiological Significance of Histone Modifications2011

    • Author(s)
      Y.Hayashi et al.
    • Organizer
      Keystone Symposia-Histone Code: Fact or Fiction?
    • Place of Presentation
      Utah, USA
    • Year and Date
      2011-01-12
    • Related Report
      2011 Final Research Report
  • [Presentation] Network-Based Histone "Modification Web" Theory and "DESS" Strategy for Elucidating the Physiological Significance of Histone Modifications2011

    • Author(s)
      Y.Hayashi, et al
    • Organizer
      Keystone Symposia-Histone Code : Fact or Fiction?
    • Place of Presentation
      Utah, USA
    • Year and Date
      2011-01-12
    • Related Report
      2010 Annual Research Report
  • [Presentation] 生化学を基軸に独創性、そして独走性を目指した30年に及ぶ 遺伝子制御研究2011

    • Author(s)
      堀越 正美
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      京都
    • Related Report
      2011 Annual Research Report
    • Invited
  • [Presentation] 遺伝子制御のON/OFF:要素からネットワーク構造へ2010

    • Author(s)
      堀越正美
    • Organizer
      BMB2010(第83回日本生化学会大会・第33回日本分子生物学会年会)
    • Place of Presentation
      神戸ホ゜ートアイラント゛(神戸市)
    • Year and Date
      2010-12-10
    • Related Report
      2011 Final Research Report
  • [Presentation] ON/OFF on gene regulation : from component to network structure遺伝子制御のON/OFF:要素からネットワーク構造へ2010

    • Author(s)
      堀越正美
    • Organizer
      BMB2010(第83回日本生化学会大会・第33回日本分子生物学会年会)
    • Place of Presentation
      神戸ポートアイランド、神戸市
    • Year and Date
      2010-12-10
    • Related Report
      2010 Annual Research Report
  • [Presentation] Regulatory mechanisms of chromatin structure and function2010

    • Author(s)
      M.Horikoshi
    • Organizer
      Global Biomarker Conference
    • Place of Presentation
      Vancouver, Canada
    • Year and Date
      2010-09-10
    • Related Report
      2011 Final Research Report
  • [Presentation] Regulatory mechanisms of chromatin structure and function2010

    • Author(s)
      M.Horikoshi
    • Organizer
      2010 Global Biomarker Conference
    • Place of Presentation
      Vancouver, Canada
    • Year and Date
      2010-09-10
    • Related Report
      2010 Annual Research Report
  • [Presentation] ヒストンコード仮説の問題点と克服2009

    • Author(s)
      堀越正美
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Year and Date
      2009-12-12
    • Related Report
      2011 Final Research Report
  • [Presentation] ヒストンコード仮説の問題点と克服2009

    • Author(s)
      堀越正美
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜、横浜市
    • Year and Date
      2009-12-12
    • Related Report
      2009 Annual Research Report
  • [Presentation] ヒストン点変異体を用いた網羅的機能解析によるヌクレオソーム構造変換反応機構の構築2009

    • Author(s)
      堀越正美
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸ホ゜ートアイラント゛(神戸市)
    • Year and Date
      2009-10-23
    • Related Report
      2011 Final Research Report
  • [Presentation] ヒストン点変異体を用いた網羅的機能解析によるヌクレオソーム構造変換反応機構の構築2009

    • Author(s)
      堀越正美
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸ポートアイランド、神戸市
    • Year and Date
      2009-10-23
    • Related Report
      2009 Annual Research Report
  • [Presentation] ヒストンコード仮説の問題点と克服2009

    • Author(s)
      堀越正美
    • Organizer
      第9回日本蛋白質科学会年会
    • Place of Presentation
      全日空ホテルニュースカイ(熊本市)
    • Year and Date
      2009-05-20
    • Related Report
      2011 Final Research Report
  • [Presentation] ヒストンコード仮説の問題点と克服2009

    • Author(s)
      堀越正美
    • Organizer
      第9回日本蛋白質科学会年会
    • Place of Presentation
      全日空ホテルニュースカイ、熊本市
    • Year and Date
      2009-05-20
    • Related Report
      2009 Annual Research Report
  • [Book] スーパーサイエンスハイスクール講義-LETITBEORNOT2009

    • Author(s)
      堀越正美
    • Total Pages
      254
    • Publisher
      培風館
    • Related Report
      2011 Final Research Report
  • [Book] スーパーサイエンスハイスクール講義-LET IT BE OR NOT2009

    • Author(s)
      堀越正美
    • Total Pages
      254
    • Publisher
      培風館
    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

      http://www.iam.u-tokyo.ac.jp/homasami/etc.html

    • Related Report
      2011 Final Research Report

URL: 

Published: 2009-04-01   Modified: 2016-04-21  

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