title: Early B cell factor is an activator of the B lymphoid kinase promoter in early B cell development.
abstract: Early B cell factor (EBF) is a transcription factor suggested to be involved in the transcriptional control of several B cell restricted genes. EBF is also essential for B lymphocyte development because mice carrying a homologous disruption of the EBF gene lack mature B lymphocytes. This makes the identification of genetic targets for EBF important for the understanding of early B cell development. Examination of the nucleotide sequence of the B lymphoid kinase (Blk) promoter suggested the presence of an EBF binding site, and in vivo footprinting analysis showed that the site was protected from methylation in a pre-B cell line. EMSA indicated that recombinant and cellular EBF interact physically with this site; furthermore, transient transfections indicated that ectopic expression of EBF in nonlymphoid HeLa cells activate a Blk promoter-controlled reporter construct 9-fold. The defined EBF binding site was also important for the function of the Blk promoter in pre-B cells, because transient transfections of a reporter construct under the control of an EBF site-mutated Blk promoter displayed only 20-30% of the activity of the wild-type promoter. Furthermore, transient transfections in HeLa cells proposed that EBF and B cell-specific activator protein were able to cooperate in the activation of a Blk promoter-controlled reporter construct. These data indicate that EBF plays an important role in the regulation of the Blk promoter in early B cell development and that EBF and BSAP are capable to act in cooperation to induce a target gene.
authors.affiliation: Immunology Group, Cell and Molecular Biology, Lund University, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Akerblad
authors.forename: M
authors.initials: M
authors.lastname: Sigvardsson
mesh_terms: D001402:B-Lymphocytes / Q000166:cytology* / Q000201:enzymology*; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D004357:Drug Synergism; D004789:Enzyme Activation / Q000235:genetics / Q000276:immunology; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D051757:PAX5 Transcription Factor; D011401:Promoter Regions, Genetic / Q000276:immunology*; D013234:Stem Cells / Q000201:enzymology / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors; D014162:Transfection; D019061:src-Family Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C081976:EBF1 protein, human; D009687:Nuclear Proteins; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C082599:protein-tyrosine kinase p55(blk); D019061:src-Family Kinases