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

Authors
  • Yc, Lin
  • S, Jhunjhunwala
  • C, Benner
  • S, Heinz
  • E, Welinder
  • R, Mansson
  • M, Sigvardsson
  • J, Hagman
  • Ca, Espinoza
  • J, Dutkowski
  • Trey Ideker
  • Ck, Glass
  • C, Murre
Type
Published Article
Journal
Nature Immunology
Publisher
Springer Nature
Volume
11
Issue
7
Pages
635–643
Identifiers
DOI: 10.1038/ni.1891
Source
Ideker Lab
License
Unknown

Abstract

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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