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Nat Immunol. 2010 Jul;11(7):635-43. doi: 10.1038/ni.1891. Epub 2010 Jun 13.

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

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Department of Molecular Biology, University of California, San Diego, La Jolla, California, USA.


It is now established that the transcription factors E2A, EBF1 and Foxo1 have 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 sequences. These associations were dynamic during developmental progression. Occupancy by the E2A isoform E47 directly resulted in greater abundance, as well as a pattern of monomethylation of histone H3 at lysine 4 (H3K4) across putative enhancer regions. Finally, we divided the pro-B cell epigenome into clusters of loci with occupancy by E2A, EBF and Foxo1. From this analysis we constructed a global network consisting of transcriptional regulators, signaling and survival factors that we propose orchestrates B cell fate.

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