A CREB site in the BRCA1 proximal promoter acts as a constitutive transcriptional element.
Transcriptional regulation of the BRCA1 proximal promoter has been suggested to play a role in the decreased expression of BRCA1 observed in sporadic breast cancer. Computer analysis of the sequence of the proximal promoter reveals the presence of a potential CREB site. We have identified CREB/ATF-1 as the factor interacting with this site in nuclear extracts from MCF-7 and T-47D cells. This site is shown to be important for the constitutive expression of the promoter in these cells, as well as in Hep G2 cells. Despite the presence of this site, the BRCA1 promoter is not responsive to cAMP induction. It appears that CREB acts as a constitutive positive element for BRCA1 expression and that any mechanism inactivating CREB function would have a dramatic effect on BRCA1 expression.
Atlas
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Cancer Research Laboratories, Department of Biochemistry, Queen's University, Kingston, Ontario, Canada.
Stramwasser
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Mueller
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CR
D051697:Activating Transcription Factor 1; D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D001483:Base Sequence; D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology; D005576:Colforsin / Q000494:pharmacology; D018899:CpG Islands; D000242:Cyclic AMP / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000737:chemistry / Q000378:metabolism*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins; D019281:Dimerization; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics*; D019398:Genes, BRCA1; D017930:Genes, Reporter; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects
D051697:Activating Transcription Factor 1; D017362:Cyclic AMP Response Element-Binding Protein; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D014157:Transcription Factors; D005576:Colforsin; D000242:Cyclic AMP