A global network of transcription factors, involving E2A, EBF1 and Foxo1, that orchestrates B cell fate.
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.
Lin
Yin C
YC
Department of Molecular Biology, University of California, San Diego, La Jolla, California, USA.
Jhunjhunwala
Suchit
S
Benner
Christopher
C
Heinz
Sven
S
Welinder
Eva
E
Mansson
Robert
R
Sigvardsson
Mikael
M
Hagman
James
J
Espinoza
Celso A
CA
Dutkowski
Janusz
J
Ideker
Trey
T
Glass
Christopher K
CK
Murre
Cornelis
C
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D019070:Cell Lineage; D002478:Cells, Cultured; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D006657:Histones / Q000378:metabolism; D038041:Lymphopoiesis / Q000235:genetics; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054448:Precursor Cells, B-Lymphoid / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D050436:Regulatory Elements, Transcriptional / Q000235:genetics; D051820:TCF Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D058125:Transcription Factor 7-Like 1 Protein
D051792:Basic Helix-Loop-Helix Proteins; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D006657:Histones; D051820:TCF Transcription Factors; D015534:Trans-Activators; D058125:Transcription Factor 7-Like 1 Protein; C489921:Ebf1 protein, mouse; C467200:Foxo1 protein, mouse; C075668:Tcf3 protein, mouse; C544913:Tcf7l1 protein, mouse