Early B Cell Factor 1 Regulates B Cell Gene Networks by Activation, Repression, and Transcription- Independent Poising of Chromatin

SummaryThe transcription factor early B cell factor-1 (Ebf1) is a key determinant of B lineage specification and differentiation. To gain insight into the molecular basis of Ebf1 function in early-stage B cells, we combined a genome-wide ChIP sequencing analysis with gain- and loss-of-function transcriptome analyses. Among 565 genes that are occupied and transcriptionally regulated by Ebf1, we identified large sets involved in (pre)-B cell receptor and Akt signaling, cell adhesion, and migration. Interestingly, a third of previously described Pax5 targets was found to be occupied by Ebf1. In addition to Ebf1-activated and -repressed genes, we identified targets at which Ebf1 induces chromatin changes that poise the genes for expression at subsequent stages of differentiation. Poised chromatin states on specific targets could also be established by Ebf1 expression in T cells but not in NIH 3T3 cells, suggesting that Ebf1 acts as a “pioneer” factor in a hematopoietic chromatin context.

► Genome-wide ChIP-seq analysis of Ebf1 binding identifies target genes in pro-B cells ► Gain- and loss-of-function studies show regulation of multiple gene networks by Ebf1 ► Ebf1 induces changes in chromatin to poise target genes for expression