Cutting Edge: SWI/SNF Mediates Antisense Igh Transcription and Locus-Wide Accessibility in B Cell Precursors

Abstract

The stepwise process of Ag receptor gene assembly, termed V(D)J recombination, is coordinated during lymphocyte development by sweeping changes in chromatin that permit or deny access to a single recombinase enzyme. We now show that switching/sucrose nonfermenting (SWI/SNF) chromatin remodeling complexes are recruited to the Igh locus by an enhancer-dependent process and that these complexes are essential for generating recombinase accessibility throughout the locus. Depletion of SWI/SNF in pro-B cells also inhibits antisense transcription through all clusters of Igh gene segments, a pioneering process that has been implicated in the initial opening of chromatin. We conclude that SWI/SNF complexes play multiple roles in Igh gene assembly, ranging from initial locus activation to the spreading and maintenance of chromatin accessibility over large VH, DH, and JH domains.