Regulation of T cell receptor beta allelic exclusion at a level beyond accessibility.
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.
Duke Scholars
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Related Subject Headings
- Transcription, Genetic
- Thymus Gland
- Receptors, Antigen, T-Cell, alpha-beta
- Nucleosomes
- Mice, Knockout
- Mice
- Immunology
- Histones
- Gene Rearrangement, T-Lymphocyte
- Chromatin
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Transcription, Genetic
- Thymus Gland
- Receptors, Antigen, T-Cell, alpha-beta
- Nucleosomes
- Mice, Knockout
- Mice
- Immunology
- Histones
- Gene Rearrangement, T-Lymphocyte
- Chromatin