Early B cell factor 1 regulates B cell gene networks by activation, repression, and transcription- independent poising of chromatin.
The transcription factor early B cell factor-1 (Ebf1) is a key determinant of B lineage specification and differentiation. To gain insight into the molecular basis of Ebf1 function in early-stage B cells, we combined a genome-wide ChIP sequencing analysis with gain- and loss-of-function transcriptome analyses. Among 565 genes that are occupied and transcriptionally regulated by Ebf1, we identified large sets involved in (pre)-B cell receptor and Akt signaling, cell adhesion, and migration. Interestingly, a third of previously described Pax5 targets was found to be occupied by Ebf1. In addition to Ebf1-activated and -repressed genes, we identified targets at which Ebf1 induces chromatin changes that poise the genes for expression at subsequent stages of differentiation. Poised chromatin states on specific targets could also be established by Ebf1 expression in T cells but not in NIH 3T3 cells, suggesting that Ebf1 acts as a "pioneer" factor in a hematopoietic chromatin context.
Treiber
Thomas
T
Max Planck Institute of Immunobiology, Department of Cellular and Molecular Immunology, Stuebeweg 51, 79108 Freiburg, Germany.
Mandel
Elizabeth M
EM
Pott
Sebastian
S
Györy
Ildiko
I
Firner
Sonja
S
Liu
Edison T
ET
Grosschedl
Rudolf
R
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D019070:Cell Lineage; D002843:Chromatin / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002874:Chromosome Mapping; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D041681:NIH 3T3 Cells; D051757:PAX5 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D015398:Signal Transduction
D002843:Chromatin; D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse