title: The BRG1 chromatin remodeler regulates widespread changes in gene expression and cell proliferation during B cell activation.
abstract: Widespread changes in gene expression underlie B cell development and activation, yet our knowledge of which chromatin-remodeling factors are essential is limited. Here, we demonstrate that the BRG1 catalytic subunit of SWI/SNF complexes was dispensable for murine B cell development but played an important, albeit selective, role during activation. Although BRG1 was dispensable for CD69 induction and differentiation into plasma cells based on the ability of mutant B cells to undergo hypertrophy and secrete IgM antibodies, it was required for robust cell proliferation in response to activation. Accordingly, BRG1 was required for only ∼100 genes to be expressed at normal levels in naïve B cells but >1,000 genes during their activation. BRG1 upregulated fivefold more genes than it downregulated, and the toll-like receptor pathway and JAK/STAT cytokine-signaling pathways were particularly dependent on BRG1. The importance of BRG1 in B cell activation was underscored by the occurrence of opportunistic Pasteurella infections in conditionally mutant mice. B cell activation has long served as a model of inducible gene expression, and the results presented here identify BRG1 as a chromatin-remodeling factor that upregulates the transcriptome of B cells during their activation to promote rapid cell proliferation and to mount an effective immune response.
authors.affiliation: Department of Genetics and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Darcy W
authors.initials: DW
authors.lastname: Holley
authors.forename: Beezly S
authors.initials: BS
authors.lastname: Groh
authors.forename: Glenn
authors.initials: G
authors.lastname: Wozniak
authors.forename: Dallas R
authors.initials: DR
authors.lastname: Donohoe
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.forename: Virginia
authors.initials: V
authors.lastname: Godfrey
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Bultman
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics*; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D009687:Nuclear Proteins; D014157:Transcription Factors; C513194:Smarca4 protein, mouse; D004265:DNA Helicases