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Molecular mechanisms of gene-specific transcriptional regulation by histone methyl transferase

Research Project

Project/Area Number 14572142
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Human genetics
Research InstitutionKyushu University

Principal Investigator

YAMAMOTO Ken  Kyushu University, Medical Institute of Bioregulation, Associate Professor, 生体防御医学研究所, 助教授 (60274528)

Co-Investigator(Kenkyū-buntansha) FUKUI Yoshinori  Kyushu University, Medical Institute of Bioregulation, Associate Professor, 生体防御医学研究所, 助教授 (60243961)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsChromatin / Heterochromatin / HP1 / SUV39H1 / Historic methylation / SU(Z)12 / EZH2 / Polycomb / ヒストン / メチル化 / エピジェネティクス / SU39H1 / 転写制御
Research Abstract

Heterochromatin is the fraction of genome that remains condensed throughout the cell cycle, replicates in the late S phase, and is generally associated with pericentric and telomeric regions of chromosomes. Euchromatic genes placed into proximity of heterochromatin by chromosomal rearrangement or trans-recruitment will be variably, silenced, a phenomenon known as position effect variegation (PEV). The Polycomb group protein (PcG)-mediated gene silencing has often been compared with the heterochromatin-mediated one because some conserved domains observed in PcG proteins are shared with HP1 (chromodomain) and Su(var)3-9 (chromodomain and SET domain), and also because PcG proteins, like modifiers of PEV, are dosage sensitive.
In order to elucidate molecular mechanisms of heterochromatin initiation and/or maintenance by SUV39H1-HP1 and SU(Z)12-EZH2 systems, we investigated interactions of these proteins. We found that 1) self-interaction through the chromo shadow domain of HP1 is crucial for recruitment of SUV39H1 onto nucleosomes 2) PcG SU(Z)12 directly interacts with HP1 and EZH2 and represses transcription in the presence of HP1. We suggest that a role for SU(Z)12 in the maintenance of heterochromatin and/or HP1-mediated transcriptional repression of euchromatic genes by recruiting EZH2 or EED-EZH2 complex onto HP1□-bound nucleosomes.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (31 results)

All Other

All Publications (31 results)

  • [Publications] Morishima Y, et al.: "The clinical significance of human leukocyte antigen (HLA) allele compatibility in patients receiving a marrow transplant from serologically HLA-A, HLA-B, and HLA-DR matched unrelated donors."Blood. 99. 4200-4206 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoshida K, et al.: "Evidence for shared recognition of peptide ligand by a diverse panel of nonobese diabetic (NOD) mice-derived, islet-specific, diabetogenic T cell clones."Int Immunol.. 14. 1439-1447 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Remboutsika E, et al.: "The bromodomain mediates TIF l alpha-nucleosome interactions."J.Biol.Chem.. 277. 50318-50325 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamamoto K, et al.: "Self-interaction of heterochromatin protein 1 is required for direct binding to histone methyltransferase, SUV39H1."Biochem.Biophys.Res.Commun.. 301. 287-292 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sanui T, et al.: "DOCK2 is essential for antigen-induced translocation of TCR and lipid rafts, but not PKC-theta and LFA-1,in T cells."Immunity. 19. 119-129 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sanui T, et al.: "DOCK2 regulates Rac activation and cytoskeletal reorganization through interaction with ELMO1."Blood. 102. 2948-2950 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takada H, et al.: "Female agammaglobulinemia due to Bruton's tyrosine kinase deficiency caused by extremely skewed X chromosome inactivation."Blood. 103. 185-187 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamamoto K, et al.: "Polycomb group suppressor of zeste 12 links heterochromatin protein 1 alpha and enhancer of zeste 2."J.Biol.Chem.. 279. 401-406 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamamoto K, et al.: "Identification of novel MUNC13-4 mutations in familial hemophagocytic lymphohistiocytosis and functional analysis of MUNC 13-4-deficient cytotoxic T lymphocytes."J.Med.Genet.. (in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamamoto K, et al.: "The Genetics of complex thyroid diseases"Springer-Verlag. 9 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Morishima Y, et al.: "The clinical significance of human leukocyte antigen (HLA) allele compatibility in patients receiving a marrow transplant from serologically HLA-A, HLA-B, and HLA-DR matched unrelated donors."Blood. 99. 4200-4206 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoshida K., et al.: "Evidence for shared recognition of peptide ligand by a diverse panel of nonobese diabetic (NOD) mice-derived, islet-specific, diabetogenic T cell clones."Int Immunol.. 14. 1439-1447 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Remboutaika B, et al.: "The bromodomain mediates TIF 1 alpha-nucleosome interactions."J.Biol.Chem.. 277. 50318-50325 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamamoto K, et al.: "Self-interaction of heterochromatin protein 1 is required for direct binding to histone methyltransferase, SUV39H1."Biochem.Biophys.Res.Commun.. 301. 287-292 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sanui T, et al.: "DOCK2 is essential for antigen-induced translocation of TCR and lipid rafts, but not PKC-theta and LFA-1, in T cells."Immunity. 19. 119-129 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sanui T, et al.: "DOCK2 regulates Rac activation and cytoskeletal reorganization through interaction with ELMO1."Blood. 102. 2948-2950 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takada H, et al.: "Female agammaglobulinemia due to Bruton's tyrosine kinase deficiency caused by extremely skewed X chromosome inactivation."Blood. 103. 185-187 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamamoto K, et al.: "Polycomb group suppressor of zeste 12 links heterochromatin protein 1 alpha and enhancer of zeste 2."J.Biol.Chem.. 279. 401-406 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamamoto K, et al.: "Identification of novel MUNC13-4 mutations in familial hemophagocytic lymphohistiocytosis and functional analysis of MUNC13-4-deficient cytotoxic T lymphocytes."J.Med.Genet.. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamamoto K, et al.: "Springer-Verlag"The Genetics of complex thyroid diseases. 55-63 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Morishima Y, et al.: "The clinical significance of human leukocyte antigen (HLA) allele compatibility in patients receiving a marrow transplant from serologically HLA-A, HLA-B, and HLA-A-DR matched unrelated donors."Blood. 99. 4200-4206 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yoshida K, et al.: "Evidence for shared recognition of peptide ligand by a diverse panel of nonobese diabetic(NOD)mice-derived, islet-specific, diabetogenic T cell clones."Int Immunol.. 14. 1439-1447 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Remboutsika E, et al.: "The bromodomain mediates TIFlalpha-nucleosome interactions."J.Biol.Chem.. 277. 50318-50325 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamamoto K, et al.: "Self-interaction of heterochromatin protein 1 is required for direct binding to histone methyltransferase, SUV39H1."Biochem.Biophys.Res.Commun.. 301. 287-292 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Takada H, et al.: "Female agammaglobulinemia due to Bruton's tyrosine kinase deficiency caused by extremely skewed X chromosome inactivation."Blood. 103. 185-187 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamamoto K, et al.: "Polycomb group suppressor of zeste 12 links heterochromatin protein 1 alpha and enhancer of zeste 2."J.Biol.Chem.. 279. 401-406 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamamoto K, et al.: "Self-interaction of heterochromatin protein 1 is required for direct binding to histone methyltransferase, SUV39H1"Biochem.Biophys.Res.Commun.. 301(2). 287-292 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Remboutsika E, et al.: "The bromodomain mediates TIF1α-nucleosome interactions"J.Biol.Chem.. 277(52). 50318-50325 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoshida K, et al.: "Evidence for shared recognition of peptide ligand by a diverse panel of nonobese diabetic (NOD) mice-derived, islet-specific, diabetogenic T cell clones"Int.Immunol.. 14(12). 1439-1447 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Morishima Y, et al.: "The clinical significance of human leukocyte antigen (HLA) allele compatibility in patients receiving a marrow transplant from serologically HLA-A, HLA-B, and HLA-DR matched unrelated donors"Blood. 99(11). 4200-4206 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamamoto K, et al.: "HLA and Autoimmune Thyroid Diseases. The Genetics of complex thyroid diseases"T.Akamizu, M.Kasuga, TF Davies Eds. Springer-Verlag, Tokyo. 9 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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