Essential function for SWI-SNF chromatin-remodeling complexes in the promoter-directed assembly of Tcrb genes.
The assembly of genes encoding antigen receptors is regulated by developmental changes in chromatin that either permit or deny access to a single variable-(diversity)-joining recombinase. These changes are guided by transcriptional promoters and enhancers, which serve as accessibility-control elements in antigen-receptor loci. The function of each accessibility-control element and the factors they recruit to remodel chromatin remain obscure. Here we show that the recruitment of SWI-SNF chromatin-remodeling complexes compensated for the accessibility-control element function of a promoter but not an enhancer of the T cell receptor-beta locus (Tcrb). Loss of SWI-SNF function in thymocytes inactivated recombinase targets at the endogenous Tcrb locus. Thus, initiation of Tcrb gene assembly and T cell development is contingent on the recruitment of SWI-SNF to promoters, which exposes gene segments to variable-(diversity)-joining recombinase.
Osipovich
Oleg
O
Department of Microbiology and Immunology, Vanderbilt University, Nashville, Tennessee 37232, USA.
Cobb
Robin Milley
RM
Oestreich
Kenneth J
KJ
Pierce
Steven
S
Ferrier
Pierre
P
Oltz
Eugene M
EM
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002843:Chromatin / Q000235:genetics; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D015870:Gene Expression / Q000276:immunology*; D015329:Gene Rearrangement, T-Lymphocyte; D019674:Genes, T-Cell Receptor beta; D015151:Immunoblotting; D047468:Immunoprecipitation; D051379:Mice; D009707:Nucleosomes / Q000235:genetics; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism*
D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D009707:Nucleosomes; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors