Transcription factor EBF restricts alternative lineage options and promotes B cell fate commitment independently of Pax5.
Alternative lineage restriction and B cell fate commitment require the transcription factor Pax5, but the function of early B cell factor (EBF) in these processes remains mostly unexplored. Here we show that in the absence of EBF, 'expandable' and clonal lymphoid progenitor cells retained considerable myeloid potential. Conversely, ectopic expression of EBF in multipotential progenitor cells directed B cell generation at the expense of myeloid cell fates. EBF induced Pax5 and antagonized expression of genes encoding the transcription factors C/EBPalpha, PU.1 and Id2. Notably, sustained expression of EBF in Pax5-/- hematopoietic progenitor cells was sufficient to block their myeloid and T lineage potential in vivo. Furthermore, in Pax5-/- pro-B cells, higher EBF expression repressed alternative lineage genes. Thus, EBF can restrict alternative lineage 'choice' and promote commitment to the B cell fate independently of Pax5.
Pongubala
Jagan M R
JM
Howard Hughes Medical Institute, Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, Illinois 60637, USA.
Northrup
Daniel L
DL
Lancki
David W
DW
Medina
Kay L
KL
Treiber
Thomas
T
Bertolino
Eric
E
Thomas
Matthew
M
Grosschedl
Rudolf
R
Allman
David
D
Singh
Harinder
H
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000378:metabolism; D019070:Cell Lineage / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015536:Down-Regulation; D018507:Gene Expression Regulation, Developmental; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology; D051757:PAX5 Transcription Factor / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000276:immunology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D000099232:Proto-Oncogene Protein Spi-1
D022763:CCAAT-Enhancer-Binding Protein-alpha; D004268:DNA-Binding Proteins; D051757:PAX5 Transcription Factor; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1; C489921:Ebf1 protein, mouse; C497282:Pax5 protein, mouse