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Structural and functional analyses of a histone demethylase that regulates cell differentiation

Research Project

Project/Area Number 23770131
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Structural biochemistry
Research InstitutionThe Institute of Physical and Chemical Research

Principal Investigator

SENGOKU Toru  独立行政法人理化学研究所, 横山構造生物学研究室, 研究員 (60576312)

Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
KeywordsX線結晶構造解析 / エピジェネティクス / 分化 / ケミカルバイオロジー / スクリーニング
Research Abstract

Functions of eukaryotic chromatin are regulated by various post-translational modification. Methylations of histone lysine residues have distinct functions depending on their positions: H3K27 trimethylation (H3K27me3) marks repressive genes. UTX/KDM6A is an H3K27 specific demethylase involved in animal cell differentiation and cell fate decision.
To elucidate the structural basis for H3K27 specific demethylation by UTX, we determined the crystal structure of its H3 complex, which showed that UTX contains a novel zinc-binding domain in its C-terminus as well as the catalytic Jumonji domain. The jumonji domain accommodates H3 residues around H3K27, whereas the zinc-binding domain recognizes H3L20 and its neighboring residues. Biochemical analysis of mutant UTX showed that these interactions are required for demethylation. Our study

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (9 results)

All 2013 2012 2011 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (6 results) Remarks (1 results)

  • [Journal Article] UTX and UTY Demonstrate Histone Demethylase-Independent Function in Mouse Embryonic Development2012

    • Author(s)
      Karl B. Shpargel, Toru Sengoku, Shigeyuki Yokoyama, Terry Magnuson
    • Journal Title

      PLOS genetics

      Volume: 8 Issue: 9 Pages: e1002964-e1002964

    • DOI

      10.1371/journal.pgen.1002964

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Structural basis for histone H3 Lys 27 demethylation by UTX/KDM6A2011

    • Author(s)
      Sengoku T, Yokoyama S
    • Journal Title

      Genes Dev

      Volume: 25(21) Issue: 21 Pages: 2266-77

    • DOI

      10.1101/gad.172296.111

    • Related Report
      2013 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Presentation] Structural Basis for Histone H3 Lys27 demethylation by UTX/KDM6A2013

    • Author(s)
      Toru Sengoku and Shigeyuki Yokoyama
    • Organizer
      Fujihara Seminar
    • Place of Presentation
      苫小牧
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] Structural Basis for Histone H3 Lys27 demethylation by UTX/KDM6A2013

    • Author(s)
      Toru Sengoku and Shigeyuki Yokoyama
    • Organizer
      ICSG2013
    • Place of Presentation
      札幌
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] Structural Basis for Histone H3 Lys27 demethylation by UTX/KDM6A2011

    • Author(s)
      仙石徹、横山茂之
    • Organizer
      日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2011-12-16
    • Related Report
      2013 Final Research Report
  • [Presentation] Structural Basis for Histone H3 Lys27 demethylation by UTX/KDM6A2011

    • Author(s)
      仙石徹、横山茂之
    • Organizer
      日本エピジェネティクス研究会年会
    • Place of Presentation
      熊本
    • Year and Date
      2011-05-20
    • Related Report
      2013 Final Research Report
  • [Presentation] Structural Basis for demethylation of Histone H3 Lys27 by UTX/KDM6A2011

    • Author(s)
      仙石徹、横山茂之
    • Organizer
      第5回日本エピジェネティクス研究会年会
    • Place of Presentation
      KKRホテル熊本
    • Related Report
      2011 Research-status Report
  • [Presentation] Structural Basis for demethylation of Histone H3 Lys27 by UTX/KDM6A2011

    • Author(s)
      Toru Sengoku, Shigeyuki Yokoyama
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2011 Research-status Report
  • [Remarks] 理化学研究所のホームページ 本研究成果発表のプレスリリースを行った。

    • URL

      http://www.riken.jp/pr/press/2011/20111014/

    • Related Report
      2013 Final Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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