Cutting edge: SWI/SNF mediates antisense Igh transcription and locus-wide accessibility in B cell precursors.
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 V(H), D(H), and J(H) domains.
Osipovich
Oleg A
OA
Department of Microbiology and Immunology, Vanderbilt University, Nashville, TN 37232, USA.
Subrahmanyam
Ramesh
R
Pierce
Steven
S
Sen
Ranjan
R
Oltz
Eugene M
EM
D000818:Animals; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D016373:DNA, Antisense / Q000235:genetics; D004742:Enhancer Elements, Genetic; D050438:Genes, Immunoglobulin Heavy Chain / Q000235:genetics*; D051379:Mice; D054448:Precursor Cells, B-Lymphoid / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D045567:VDJ Recombinases / Q000378:metabolism
D002868:Chromosomal Proteins, Non-Histone; D016373:DNA, Antisense; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors; D045567:VDJ Recombinases