title: EBP1 is a novel E2F target gene regulated by transforming growth factor-β.
abstract: Regulation of gene expression requires transcription factor binding to specific DNA elements, and a large body of work has focused on the identification of such sequences. However, it is becoming increasingly clear that eukaryotic transcription factors can exhibit widespread, nonfunctional binding to genomic DNA sites. Conversely, some of these proteins, such as E2F, can also modulate gene expression by binding to non-consensus elements. E2F comprises a family of transcription factors that play key roles in a wide variety of cellular functions, including survival, differentiation, activation during tissue regeneration, metabolism, and proliferation. E2F factors bind to the Erb3-binding protein 1 (EBP1) promoter in live cells. We now show that E2F binding to the EBP1 promoter occurs through two tandem DNA elements that do not conform to typical consensus E2F motifs. Exogenously expressed E2F1 activates EBP1 reporters lacking one, but not both sites, suggesting a degree of redundancy under certain conditions. E2F1 increases the levels of endogenous EBP1 mRNA in breast carcinoma and other transformed cell lines. In contrast, in non-transformed primary epidermal keratinocytes, E2F, together with the retinoblastoma family of proteins, appears to be involved in decreasing EBP1 mRNA abundance in response to growth inhibition by transforming growth factor-β1. Thus, E2F is likely a central coordinator of multiple responses that culminate in regulation of EBP1 gene expression, and which may vary depending on cell type and context.
authors.affiliation: Department of Physiology and Pharmacology, Children Health Research Institute and Lawson Health Research Institute, University of Western Ontario, London, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Judah
authors.forename: Wing Y
authors.initials: WY
authors.lastname: Chang
authors.forename: Lina
authors.initials: L
authors.lastname: Dagnino
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D050684:E2F Transcription Factors / Q000235:genetics / Q000378:metabolism*; D050687:E2F1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C101633:PA2G4 protein, human; D016601:RNA-Binding Proteins; D016212:Transforming Growth Factor beta; D008156:Luciferases