The BRG1 Chromatin Remodeler Regulates Widespread Changes in Gene Expression and Cell Proliferation During B Cell Activation. Issue 1 (23rd September 2013)

• Record Type: Journal Article
• Authors: Holley, Darcy W.; Groh, Beezly S.; Wozniak, Glenn; Donohoe, Dallas R.; Sun, Wei; Godfrey, Virginia; Bultman, Scott J.
• Is Part Of: Journal of cellular physiology. Volume 229:Issue 1(2014:Jan.)
• Page Start: 44
• Page End: 52
• Publication Date: 2013-09-23
• Subjects: Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.24414
• Languages: English
• ISSNs: 0021-9541

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="jcp24414-sec-0001" sec-type="section"> <p>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 <italic>Pasteurella</italic> 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. J. Cell. Physiol. 229: 44–52, 2014. © 2013 Wiley Periodicals, Inc.</p> </sec> </abstract>