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Early B-cell factor, E2A, and Pax-5 coop ... y B cell-specific mb-1 promoter
Early B-cell factor, E2A, and Pax-5 cooperate to activate the early B cell-specific mb-1 promoter
5441
Previous studies have suggested that the early-B-cell-specific mb-1(Igalpha) promoter is regulated by EBF and Pax-5. Here, we used in vivo footprinting assays to detect occupation of binding sites in endogenous mb-1 promoters at various stages of B-cell differentiation. In addition to EBF and Pax-5 binding sites, we detected occupancy of a consensus binding site for E2A proteins (E box) in pre-B cells. EBF and E box sites are crucial for promoter function in transfected pre-B cells, and EBF and E2A proteins synergistically activated the promoter in transfected HeLa cells. Other data suggest that EBF and E box sites are less important for promoter function at later stages of differentiation, whereas binding sites for Pax-5 (and its Ets ternary complex partners) are required for promoter function in all mb-1-expressing cells. Using DNA microarrays, we found that expression of endogenous mb-1 transcripts correlates most closely with EBF expression and negatively with Id1, an inhibitor of E2A protein function, further linking regulation of the mb-1 gene with EBF and E2A. Together, our studies demonstrate the complexity of factors regulating tissue-specific transcription and support the concept that EBF, E2A, and Pax-5 cooperate to activate target genes in early B-cell development.
Sigvardsson M, Clark DR, Fitzsimmons D, Doyle M, Akerblad P, Breslin T, Bilke S, Li R, Yeamans C, Zhang G, Hagman J
Molecular and cellular biology
2002-12-01 00:00
22
24
8539-51
Animals,Antigens, CD,Antigens, CD79,B-Cell-Specific Activator Protein,B-Lymphocytes,Base Sequence,Basic Helix-Loop-Helix Transcription Factors,Binding Sites,Cell Line,DNA Footprinting,DNA-Binding Proteins,Gene Expression Regulation,Genes, Reporter,Helix-Loop-Helix Motifs,Humans,Macromolecular Substances,Mice,Molecular Sequence Data,Mutation,Nuclear Proteins,Oligonucleotide Array Sequence Analysis,Promoter Regions (Genetics),Protein Binding,Receptors, Antigen, B-Cell,Recombinant Fusion Proteins,Trans-Activators,Transcription Factors,Transcription, Genetic,Antigens, CD,Antigens, CD79,B-Cell-Specific Activator Protein,Basic Helix-Loop-Helix Transcription Factors,CD79A protein, human,Cd79a protein, mouse,DNA-Binding Proteins,EBF1 protein, human,Ebf1 protein, mouse,Macromolecular Substances,Nuclear Proteins,PAX5 protein, human,Pax5 protein, mouse,Receptors, Antigen, B-Cell,Recombinant Fusion Proteins,TCF3 protein, human,Trans-Activators,Transcription Factors
Department for Stem Cell Biology, Lund, Sweden.
Mol. Cell. Biol.
NIAID P01 AI22295, NIAID R01 AI37574, NIAID T32 AI00048
0270-7306
0
False
12446773
