Genomics

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Brg1-dependent enhancer-promoter interactions support B cell activation and germinal center formation


ABSTRACT: Activation and differentiation of B cells depend on extensive rewiring of gene expression networks through changes in chromatin structure and accessibility. The chromatin remodeling complex BAF with its catalytic subunit Brg1 was previously identified as an essential regulator of early B cell development, however, how Brg1 orchestrates gene expression during mature B cell activation is less clear. Here, we find that Brg1 is required for B cell proliferation and germinal center formation through selective interactions with enhancers. Brg1 recruitment to enhancers was associated with increased chromatin accessibility and transcriptional activation of their coupled promoters following B cell activation and expression of cell cycle-associated genes. Accordingly, Brg1-deficient B cells were unable to mount germinal center reactions and support the formation of class-switch plasma cells. Our findings show that changes in B cell transcriptomes that support cell proliferation and GC formation depend on enhancer activation by Brg1. Thus, the BAF complex plays a critical role during the onset of the humoral immune response. Overall design: RNA-seq and ATAC-seq of activated B cells, harvested after 96 hours activation using LPS and IL-4.

INSTRUMENT(S): Illumina NextSeq 500 (Mus musculus)

ORGANISM(S): Mus musculus  

SUBMITTER: Ziv Shulman  

PROVIDER: GSE180994 | GEO | 2021-08-21

REPOSITORIES: GEO

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GSE180994_Brg1_Deseq_results.xlsx Xlsx
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