Transcriptional regulation of the murine brca2 gene by CREB/ATF transcription factors

• Published in: Biochemical and biophysical research communications Vol. 312; no. 3; pp. 702 - 707
• Main Authors: Callens, Nathalie, Baert, Jean-Luc, Monté, Didier, Sunesen, Morten, Van Lint, Carine, de Launoit, Yvan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 19.12.2003
• Subjects: Activating Transcription Factors; Animals; ATF protein; Blood Proteins - genetics; Blood Proteins - metabolism; brca2; brca2 gene; BRCA2 Protein - genetics; BRCA2 Protein - metabolism; Cell Line; Cell Line, Tumor; Cyclic AMP Response Element Modulator; Cyclic AMP Response Element-Binding Protein - genetics; Cyclic AMP Response Element-Binding Protein - metabolism; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Epithelial Cells - metabolism; Gene Expression Regulation - genetics; Genes, BRCA2 - physiology; Mammary; Mice; Mouse; NIH 3T3 Cells; Promoter; Promoter Regions, Genetic - genetics; Repressor Proteins; Structure-Activity Relationship; Teratocarcinoma - genetics; Teratocarcinoma - metabolism; Transcription; Transcription Factors - genetics; Transcription Factors - metabolism; Transcriptional Activation - genetics; Promoter; Transcription; Mouse; Mammary; brca2
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2003.10.176

The brca2 gene encodes a nuclear protein which is mainly involved in DNA repair and, when mutated, is responsible for some of the hereditary breast cancers. However, brca2 expression is also deregulated in sporadic breast tumors. In the mouse brca2 gene we had earlier identified a region of 148 bp upstream of the transcription start site sufficient to activate its expression. In the present report, we show that the −92 to −40 bp region is essential for the transcription of brca2 in murine mammary cells and that this nucleotide sequence contains one putative CREB/ATF consensus site (cAMP responsive element: CRE). We demonstrated that the mutation of this binding site led to a highly significant reduction of the mouse brca2 transcription, and that CREB, CREM, and/or ATF-1 functionally bound to and regulated this promoter. Therefore, the regulation of the promoter of the mouse brca2 gene is driven by this family of transcription factors.