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Publication : Regulation of T cell receptor beta allelic exclusion at a level beyond accessibility.

First Author  Jackson A Year  2005
Journal  Nat Immunol Volume  6
Issue  2 Pages  189-97
PubMed ID  15640803 Mgi Jnum  J:95669
Mgi Id  MGI:3526765 Doi  10.1038/ni1157
Citation  Jackson A, et al. (2005) Regulation of T cell receptor beta allelic exclusion at a level beyond accessibility. Nat Immunol 6(2):189-97
abstractText  Allelic exclusion of V(beta)-to-DJ(beta) recombination depends on asynchronous rearrangement of alleles of the gene encoding T cell receptor beta in double-negative thymocytes and feedback inhibition that is maintained in double-positive thymocytes. Feedback is thought to be enforced through downregulation of V(beta) accessibility. In an attempt to override this negative regulation, we introduced the enhancer of the gene encoding T cell receptor alpha into the V(beta) gene cluster downstream of V(beta)12. In double-negative thymocytes, the introduced enhancer had no measurable effect on accessibility, but V(beta)12 rearrangement was stimulated and V(beta)12 allelic exclusion was partially subverted. In contrast, double-positive thymocytes showed increased V(beta) transcription and accessibility, but feedback inhibition of V(beta)-to-DJ(beta) recombination remained intact. Our results indicate additional regulatory constraints on V(beta)-to-DJ(beta) recombination that operate beyond the accessibility barrier.
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