Brg1 activates enhancer repertoires to establish B cell identity and modulate cell growth

Early B cell development is orchestrated by the combined activities of the transcriptional regulators E2A, EBF1, Foxo1 and Ikaros. However, how the genome-wide binding patterns of these regulators are modulated during B-lineage development remains to be determined. Here, we found that in lymphoid progenitors the chromatin remodeler Brg1 specified the B cell fate. In committed pro-B cells Brg1 regulated Igh locus contraction and controlled Myc expression to modulate the expression of genes that regulate ribosome biogenesis. In committed pro-B cells Brg1 suppressed a pre-B lineage-specific pattern of gene expression. Finally, we found that Brg1 acted mechanistically to establish B cell fate and modulate cell growth by facilitating access of lineage-specific transcription factors to poised enhancer repertoires.