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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism*
  • B-Lymphocytes / pathology
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Cell Lineage
  • Cells, Cultured
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors / genetics
  • Gene Expression Regulation, Developmental
  • Gene Regulatory Networks*
  • Histones / metabolism
  • Lymphopoiesis / genetics
  • Methylation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Precursor Cells, B-Lymphoid / immunology
  • Precursor Cells, B-Lymphoid / metabolism*
  • Precursor Cells, B-Lymphoid / pathology
  • Regulatory Elements, Transcriptional / genetics
  • TCF Transcription Factors / genetics
  • TCF Transcription Factors / metabolism*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcription Factor 7-Like 1 Protein


  • Basic Helix-Loop-Helix Transcription Factors
  • Ebf1 protein, mouse
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors
  • Foxo1 protein, mouse
  • Histones
  • TCF Transcription Factors
  • Tcf3 protein, mouse
  • Tcf7l1 protein, mouse
  • Trans-Activators
  • Transcription Factor 7-Like 1 Protein

Associated data

  • GEO/GSE21512
  • GEO/GSE21978