2003 Fiscal Year Final Research Report Summary
Recombination control of lymphocyte antigen receptor loci by chromati modification
| Project/Area Number |
14370056
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Kyoto University |
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Principal Investigator |
IKUTA Koichi Kyoto University, Institute for Virus Research, Professor, ウイルス研究所, 教授 (90193177)
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| 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
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| Project Period (FY) |
2002 – 2003
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| Keywords | cytokine / Stat / γδ T cell / T cell antigen receptor / signal transduction / DNA recombination / histone modification / chromatin |
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| 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.
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