Coordinate regulation of B cell differentiation by the transcription factors EBF and E2A.
The transcription factors EBF and E2A are required at a similar step in early B cell differentiation. EBF and E2A synergistically upregulate transcription of endogenous B cell-specific genes in a non-B cell line. Here, we examine a genetic collaboration between these factors in regulating B lymphopoiesis. We find that Ebf+/- E2a+/- mice display a marked defect in pro-B cell differentiation at a stage later than observed in the single homozygous mutant mice. Pro-B cells from Ebf+/- E2a+/- mice show reduced expression of lymphoid-specific transcripts, including Pax5, Rag1, Rag2, and mb-1. We also show that EBF directly binds and activates the Pax5 promoter. Together, these data show collaboration between EBF and E2A and provide insight into the hierarchy of transcription factors that regulate B lymphocyte differentiation.
O'Riordan
M
M
Howard Hughes Medical Institute, Department of Microbiology and Immunology, University of California, San Francisco 94143, USA.
Grosschedl
R
R
D000818:Animals; D000831:Animals, Newborn; D016175:B-Lymphocyte Subsets / Q000378:metabolism / Q000473:pathology; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism* / Q000473:pathology; D001854:Bone Marrow Cells / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004742:Enhancer Elements, Genetic / Q000276:immunology; D018985:Epitopes, B-Lymphocyte / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D006580:Genetic Carrier Screening; D018257:Helix-Loop-Helix Motifs / Q000235:genetics / Q000276:immunology*; D007146:Immunoglobulin lambda-Chains / Q000235:genetics; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D051757:PAX5 Transcription Factor; D011401:Promoter Regions, Genetic / Q000276:immunology; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology; D051820:TCF Transcription Factors; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D004268:DNA-Binding Proteins; C489921:Ebf1 protein, mouse; D018985:Epitopes, B-Lymphocyte; D007146:Immunoglobulin lambda-Chains; D009687:Nuclear Proteins; D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse; D051820:TCF Transcription Factors; C544913:Tcf7l1 protein, mouse; D015534:Trans-Activators; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors