Essential function for SWI-SNF chromatin-remodeling complexes in the promoter-directed assembly of Tcrb genes

Oleg Osipovich, Robin Milley Cobb, Kenneth J. Oestreich, Steven Pierce, Pierre Ferrier, Eugene M. Oltz

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

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-β 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.

Original languageEnglish
Pages (from-to)809-816
Number of pages8
JournalNature immunology
Volume8
Issue number8
DOIs
StatePublished - Aug 1 2007

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