Regulation of T cell receptor-alpha gene recombination by transcription.
Despite the longstanding correlation between transcription and variable-(diversity)-joining (V(D)J) recombination, it is unknown whether transcription itself can direct recombinase targeting. Here we show that blockade of transcriptional elongation through the mouse T cell receptor-alpha (Tcra) locus suppressed V(alpha)-to-J(alpha) recombination and chromatin remodeling of J(alpha) segments. Transcriptional blockade also derepressed cryptic J(alpha) promoters. Our results demonstrate two key functions for transcription in Tcra locus regulation. Transcription increases the recombination of J(alpha) segments located within several kilobases of a promoter and prevents the activation of downstream promoters through transcriptional interference. These influences promote an ordered progression of Tcra locus recombination events and selection of a robust Tcra repertoire.
Abarrategui
Iratxe
I
Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Krangel
Michael S
MS
D000818:Animals; D042002:Chromatin Assembly and Disassembly; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor / Q000235:genetics*; D019673:Genes, T-Cell Receptor alpha / Q000235:genetics*; D007133:Immunoglobulin Joining Region / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D011401:Promoter Regions, Genetic; D011995:Recombination, Genetic; D017384:Sequence Deletion; D014158:Transcription, Genetic / Q000235:genetics*
D007133:Immunoglobulin Joining Region