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Recombination control of lymphocyte antigen receptor loci by chromati modification

Research Project

Project/Area Number 14370056
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionKyoto University

Principal Investigator

IKUTA Koichi  Kyoto University, Institute for Virus Research, Professor, ウイルス研究所, 教授 (90193177)

Co-Investigator(Kenkyū-buntansha) KAKAZU Naoki  Kyoto Prefectural University of Medicine, Instructor, 医学部, 助手 (20264757)
YE Sang-kyu  Kyoto University, Institute for Virus Research, JSPS Postdoctoral Fellowship for Foreign Researchers, ウイルス研究所, 日本学術振興会外国人特別研究員
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 2003: ¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 2002: ¥7,700,000 (Direct Cost: ¥7,700,000)
Keywordscytokine / Stat / γδ T cell / T cell antigen receptor / signal transduction / DNA recombination / histone modification / chromatin / サイトカイン / ヒストン修飾 / クロマチン / サイトカインレセプタ
Research Abstract

The IL-7 receptor (IL-7R) plays several critical roles in lymphocyte development by promoting proliferation and by inducing V(D)J,recombination in TCR and Ig loci. Previously, we have shown that Stat5 activated by the IL-7R binds to Jγ germline promoter and induces germline transcription of the TCRγ locus. An active Stat5 also rescued germline transcription and V-J recombination of this locus in IL-7Rα-/-thymocytes. To identify the molecular mechanism that links the Stat5-induced germline transcription to the accessibility,of the TCRγ locus, we characterized the role of transcriptional coactivators and histone acetylation. Our results demonstrated that CBP/p300 transcriptional,coactivators augment Stat5-induced germline transcription of the TCRγ locus by their intrinsic histone acetyltransferase activity. Concurrently, histones are hyperacetylated at transcriptionally-active Jγ segments in normal thymocyte precursors and Ba/F3 cells, but not in IL-7Rα-l-thymocytes. Cytokine stimulation rapidly induces the recruitment of Stat5 and histone acetylation at the endogenous Jγ segments in Ba/F3 cells. We also showed that forced expression of RAG1 and RAG2 selectively induces cleavage at the Jγ segment in Ba/F3 cells. Therefore, our study strongly supported the idea that Stat5 recruits the transcriptional coactivators to the Jγ germline promoter and controls the accessibility of the TCRγ locus by histone acetylation.

Report

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

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Lee, H.-C.: "Seeding of dendritic epidermal T cells in the neonatal skin is reduced in 129 strain of mice."Immunol.Lett.. 81. 211-216 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Han, H.: "Inducible gene knockout of transcription factor recombination signal binding protein-J reveals its essential role in T versus B lineage decision."Int.Immunol.. 14. 637-645 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Watanabe, N.: "Activation and differentiation of autoreactive B-1 cells by interleukin-10 induce autoimmune hemolytic anemia in Fas-deficient anti-erythrocyte immunoglobulin transgenic mice."J.Exp.Med.. 196. 141-146 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Lahn, M.: "MHC class I-dependent Vγ4+ pulmonary T cells regulate αβ T cell-independent airway responsiveness."Proc.Natl.Acad.Sci.USA.. 99. 8850-8855 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Watanabe, N.: "Elimination of local macrophages in intestine prevents chronic colitis in interleukin-10 deficient mice."Dig.Dis.Sci.. 48. 408-418 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kim-Saijo, M.: "Generation of a transgenic animal model of hyperthyroid Graves' disease."Eur.J.Immunol.. 33. 2531-2538 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Lee, H.-C., et al.: "Seeding of dendritic epidermal T, cells in the neonatal skin is reduced in 129 strain of mice."Immunol.Lett.. 81. 211-216 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Han, H., et al.: "Inducible gene knockout of transcription factor recombination signal binding protein-J reveals its essential role in T versus B lineage decision."Int.Immunol.. 14. 637-645 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Watanabe, N., et al.: "Activation and differentiation of autoreactive B-1 cells by interleukin-10 induce autoimmune hemolytic anemia in Fas-deficient anti-erythrocyte immunoglobulin transgenic mice."J.Exp.Med.. 196. 141-146 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Lahn, M., et al.: "MHC class I-dependent Vγ4+ pulmonary T cells regulate ab T cell-independent airway responsiveness."Proc.Natl.Acad.Sci.USA.. 99. 8850-8855 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Watanabe, N., et al.: "Elimination of local macrophages in intestine prevents chronic colitis in interleukin-10 deficient mice."Dig.Dis.Sci.. 48. 408-418 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kim-Saijo, M.et al.: "Generation of a transgenic animal model of hyperthyroid Graves' disease."Eur.J.Immunol.. 33. 2531-2538 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Watanabe, N.: "Elimination of local macrophages in intestine prevents chronic colitis in interleukin-10 deficient mice"Dig.Dis.Sci.. 48. 408-418 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kim-Saijo, M.: "Generation of a transgenic animal model of hyperthyroid Graves' disease"Eur.J.Immunol.. 33. 2531-2538 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Lee, H.-C: "Seeding of dendritic epidermal T cells in the neonatal skin is reduced in 129 strain of mice"Immunol.Lett.. 81. 211-216 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Han, H: "Inducible gene knockout of transcription factor recombination signal binding protein-J reveals its essential role in T versus B lineage decision"Int.Immunol.. 14. 637-645 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Watanabe, N: "Activation and differentiation of autoreactive B-1 cells by interleukin-10 induce autoimmune hemolytic anemia in Fas-deficient anti-erythrocyte immunoglobulin transgenic mice"J.Exp.Med.. 196. 141-146 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Lahn, M: "MHC class I-dependent Vγ4+pulmonary T cells regulate αβ T cell-independent airway responsiveness"Proc.Natl.Acad.Sci. USA.. 99. 8850-8855 (2002)

    • Related Report
      2002 Annual Research Report

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

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