Induction of early B cell factor (EBF) and multiple B lineage genes by the basic helix-loop-helix transcription factor E12.
The transcription factors encoded by the E2A and early B cell factor (EBF) genes are required for the proper development of B lymphocytes. However, the absence of B lineage cells in E2A- and EBF-deficient mice has made it difficult to determine the function or relationship between these proteins. We report the identification of a novel model system in which the role of E2A and EBF in the regulation of multiple B lineage traits can be studied. We found that the conversion of 70Z/3 pre-B lymphocytes to cells with a macrophage-like phenotype is associated with the loss of E2A and EBF. Moreover, we show that ectopic expression of the E2A protein E12 in this macrophage line results in the induction of many B lineage genes, including EBF, IL7Ralpha, lambda5, and Rag-1, and the ability to induce kappa light chain in response to mitogen. Activation of EBF may be one of the critical functions of E12 in regulating the B lineage phenotype since expression of EBF alone leads to the activation of a subset of E12-inducible traits. Our data demonstrate that, in the context of this macrophage line, E12 induces expression of EBF and together these transcription factors coordinately regulate numerous B lineage-associated genes.
Department of Biology, University of California San Diego, La Jolla, California 92093, USA. bkee@biomail.ucsd.edu
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D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D001665:Binding Sites; D002460:Cell Line; D019070:Cell Lineage; D002462:Cell Membrane / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation; D018257:Helix-Loop-Helix Motifs; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007147:Immunoglobulin Light Chains; D054444:Immunoglobulin Light Chains, Surrogate; D007145:Immunoglobulin kappa-Chains / Q000378:metabolism; D007148:Immunoglobulin mu-Chains / Q000378:metabolism; D051797:Inhibitor of Differentiation Protein 2; D008070:Lipopolysaccharides / Q000494:pharmacology; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008934:Mitogens / Q000494:pharmacology; D009687:Nuclear Proteins / Q000235:genetics; D051757:PAX5 Transcription Factor; D010641:Phenotype; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics; D018123:Receptors, Interleukin / Q000235:genetics; D020395:Receptors, Interleukin-7; D012097:Repressor Proteins; D051820:TCF Transcription Factors; D015534:Trans-Activators / Q000235:genetics*; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
D015703:Antigens, CD; D004268:DNA-Binding Proteins; C081976:EBF1 protein, human; C489921:Ebf1 protein, mouse; D018398:Homeodomain Proteins; C497450:ID2 protein, human; C497452:Idb2 protein, mouse; D007147:Immunoglobulin Light Chains; D054444:Immunoglobulin Light Chains, Surrogate; D007145:Immunoglobulin kappa-Chains; D007148:Immunoglobulin mu-Chains; D051797:Inhibitor of Differentiation Protein 2; D008070:Lipopolysaccharides; D016177:Macrophage-1 Antigen; D008562:Membrane Glycoproteins; D008934:Mitogens; D009687:Nuclear Proteins; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human; C497282:Pax5 protein, mouse; C499311:RAG2 protein, human; C499308:Rag2 protein, mouse; D018123:Receptors, Interleukin; D020395:Receptors, Interleukin-7; D012097:Repressor Proteins; D051820:TCF Transcription Factors; C544912:TCF7L1 protein, human; C544913:Tcf7l1 protein, mouse; D015534:Trans-Activators; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein; D016186:Receptor, Macrophage Colony-Stimulating Factor