A global network of transcription factors, involving E2A, EBF1 and Foxo1, that orchestrates the B cell fate

It is now established that the transcription factors E2A, EBF1 and Foxo1 play critical roles in B cell development. Here we show that E2A and EBF1 bound regulatory elements present in the Foxo1 locus. E2A and EBF1 as well as E2A and Foxo1, in turn, were wired together by a vast spectrum of cis-regulatory codes. These associations were dynamic during developmental progression. Occupancy by the E2A isoform, E47, directly elevated the abundance as well as the pattern of histone H3K4 monomethylation across putative enhancer regions. Finally, the pro-B cell epigenome was divided into clusters of loci that show E2A, EBF and Foxo1 occupancy. From this analysis a global network consisting of transcriptional regulators, signaling and survival factors, was constructed that we propose orchestrates the B cell fate.