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Mechanisms regulating the target specificity of gene rearrangements in immune system

Research Project

Project/Area Number 16390077
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General medical chemistry
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

SHIMIZU Akira  Kyoto University, Graduate School of Medicine, Professor, 医学研究科, 教授 (00162694)

Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2005: ¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 2004: ¥9,100,000 (Direct Cost: ¥9,100,000)
Keywordsimmunoglobulin gene / class switching / transcriptional regulation / Id2 / NFκB / histone acetylation / Pax5 / Bcl6
Research Abstract

Experiments on the class switch recombination of Ig H chain, in which the regional chromatin status and specific regulation of each gene are able to be reproduced in vitro, and on the regulation of AID gene expression, which is essential for Ig class switch recombination were mainly done. It is shown that the chromatin region of target is opened for the recombination using the level of histone acetylation at the region as the general indicator of chromatin status.
By adding HDAC inhibitor together with the repression signal for the germline transcription, the hyper-acetylation status of the target region chromatin could be maintained. Even though the target chromatin was kept open in such away, it was not able to make it the target for the recombination. This result indicates that the germline transcription occurring prior to the recombination is not simply the result of the chromatin opening but it directly involved in the process and therefore essential to make the gene the target. Moreover, results suggesting that the release from specific transcriptional repression occurs in B lymphocyte during the activation of AID gene expression were also obtained.
In addition, the oligonucleotide containing CpG array was found to repress the class switch recombination to IgG1 and IgE through the repression of germline transcription. The molecular mechanism for this was analyzed by using B lymphocytes from knockout mice of the genes that might be involved in this repression. The results indicate that Id2 and Bcl6 that repress E2A and STAT6 respectively are not involved in this process, but it is mediated by the signals through NFκB and IRF4.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (23 results)

All 2006 2005 2004

All Journal Article (23 results)

  • [Journal Article] A transmwmbrane chemokine, CXC chemokine ligand 16, expressed by lymph node fibroblastic reticular cells has the potential to regulate T cell migration and adhesion.2006

    • Author(s)
      Hara, T. et al.
    • Journal Title

      Int Immunol. 18・2

      Pages: 301-311

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A transmwmbrane chemokine, CXC chemokine ligand 16, expressed by lymph node fibroblastic reticular cells has the potential to regulate T cell migration and adhesion.2006

    • Author(s)
      Hara, T., Katakai, T., Lee, J.-H., Nambu, Y., Nakajima-Nagata, N., Gonda, H., Sugai, M., Shimizu, A.
    • Journal Title

      Internat.Immunol. 18

      Pages: 301-311

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Choroid plexus ependymal cells host neural progenitor cells in the rat.2006

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

      Glia 53・1

      Pages: 32-42

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A transmwmbrane chemokine, CXC chemokine ligand 16, expressed by lymph node fibroblastic reticular cells has the potential to regulate T cell migration and adhesion.2006

    • Author(s)
      Hara, T.et al.
    • Journal Title

      Int Immunol. 18・2

      Pages: 301-311

    • Related Report
      2005 Annual Research Report
  • [Journal Article] CpG inhibits IgE class switch recombination through suppression of NFkB activity, but not through Id2 or Bc16.2005

    • Author(s)
      Kusunoki, T. et al.
    • Journal Title

      Biochem. Biophys. Res. Comm. 238・2

      Pages: 499-506

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Accessibility control of recombination at immunoglobulin locus.2005

    • Author(s)
      Sugai, M. et al.
    • Journal Title

      Curr. Immunol. Rev. 1・1

      Pages: 69-79

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] SPINK5 polymorphism is associated with disease severity and food allergy in children with atopic dermatitis.2005

    • Author(s)
      Kusunoki, T. et al.
    • Journal Title

      J. Allergy Clin. Immunol. 115・3

      Pages: 636-638

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] CpG inhibits IgE class switch recombination through suppression of NFκB activity, but not through Id2 or Bcl6.2005

    • Author(s)
      Kusunoki, T., Sugai, M., Gonda, H., Nambu, Y., Nakajima-Nagata, N., Katakai, T., Kusunoki, M., Sakamoto, A., Tokuhisa, T., Nakahata, T., Yokota, Y., Shimizu A.
    • Journal Title

      Biochem.Biophys.Res.Comm. 328

      Pages: 499-506

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Accessibility control of recombination at immunoglobulin locus.2005

    • Author(s)
      Sugai, M., Gonda, H., Nambu, Y., Yokota, Y., Shimizu A.
    • Journal Title

      Curr.Immunol.Rev. 1

      Pages: 69-79

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] SPINK5 polymorphism is associated with disease severity and food allergy in children with atopic dermatitis.2005

    • Author(s)
      Kusunoki, T., Okafuji, I., Yoshioka, T., Saito, M., Nishikomori, R., Heike, T., Sugai, M., Shimizu A., Nakahata, T.
    • Journal Title

      J.Allergy Clin.Immunol. 115

      Pages: 636-638

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] CpG inhibits IgE class switch recombination through suppression of NFκB activity, but not through Id2 or Bcl6.2005

    • Author(s)
      Kusunoki, T.et al.
    • Journal Title

      Biochem.Biophys.Res.Comm. 238・2

      Pages: 499-506

    • Related Report
      2005 Annual Research Report 2004 Annual Research Report
  • [Journal Article] Accessibility control of recombination at immunoglobulin locus.2005

    • Author(s)
      Sugai, M.et al.
    • Journal Title

      Curr.Immunol.Rev. 1・1

      Pages: 69-79

    • Related Report
      2005 Annual Research Report
  • [Journal Article] SPINK5 polymorphism is associated with disease severity and food allergy in children with atopic dermatitis.2005

    • Author(s)
      Kusunoki, T.et al.
    • Journal Title

      J.Allergy Clin.Immunol. 115・3

      Pages: 636-638

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Multiple SNPs in intron 7 of thyrotropin receptor are associated with Graves' disease.2005

    • Author(s)
      Hiratani, H.et al.
    • Journal Title

      J.Clin.Endocrinol.Metab. 90・5

      Pages: 2898-2903

    • Related Report
      2005 Annual Research Report
  • [Journal Article]2005

    • Author(s)
      Sugai, M.et al.
    • Journal Title

      Curr.Immunol.Rev. 1・1

      Pages: 69-79

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Role of Id proteins in B lymphocyte activation : new insights fromknockout mouse studies.2004

    • Author(s)
      Sugai, M. et al.
    • Journal Title

      J. Mol. Med. 82・9

      Pages: 592-599

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Lymph node fibroblastic reticular cells construct the stromal reticulum via contact with lymphocytes.2004

    • Author(s)
      Katakai, T. et al.
    • Journal Title

      J. Exp. Med. 200・6

      Pages: 783-795

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Role of Id proteins in B lymphocyte activation : new insights from knockout mouse studies.2004

    • Author(s)
      Sugai, M., Gonda, H., Nambu, Y., Yokota, Y., Shimizu A.
    • Journal Title

      J.Mol.Med. 82

      Pages: 592-599

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Lymph node fibroblastic reticular cells construct the stromal reticulum via contact with lymphocytes.2004

    • Author(s)
      Katakai, T., Hara, T., Sugai, M., Gonda, H., Shimizu A.
    • Journal Title

      J.Exp.Med. 200

      Pages: 783-795

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Role of Id proteins in B lymphocyte activation : new insights from knockout mouse studies.2004

    • Author(s)
      Sugai, M.et al.
    • Journal Title

      J.Mol.Med. 82・9

      Pages: 592-599

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Characterization of VHε gene expressed in PBL from children with atopic diseases : detection of homologous V_H1-69 derived transcripts from three unrelated patients.2004

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

      Immunol.Lett. 94・1-2

      Pages: 99-106

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Lymph node fibroblastic reticular cells construct the stromal reticulum via contact with lymphocytes.2004

    • Author(s)
      Katakai, T.et al.
    • Journal Title

      J.Exp.Med. 200・6

      Pages: 783-795

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Roles of phospho-ERM and Rho-ROCK signaling in lymphocyte polarity and uropod formation.2004

    • Author(s)
      Lee, J.-H.et al.
    • Journal Title

      J.Cell Biol. 167・2

      Pages: 327-337

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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