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<p>Abstract</p> <p>Background</p> <p>The <it>BRCA1 </it>gene plays an important role in the maintenance of genomic stability. BRCA1 inactivation contributes to breast cancer tumorigenesis. An increasing number of transcription factors have been shown to regulate <it>BRCA1 </it>expression. c-Myc can act as a transcriptional activator, regulating up to 15% of all genes in the human genome and results from a high throughput screen suggest that <it>BRCA1 </it>is one of its targets. In this report, we used cultured breast cancer cells to examine the mechanisms of transcriptional activation of <it>BRCA1 </it>by c-Myc.</p> <p>Methods</p> <p>c-Myc was depleted using c-Myc-specific siRNAs in cultured breast cancer cells. <it>BRCA1 </it>mRNA expression and BRCA1 protein expression were determined by quantitative RT-PCR and western blot, respectively and <it>BRCA1 </it>promoter activities were examined under these conditions. DNA sequence analysis was conducted to search for high similarity to E boxes in the <it>BRCA1 </it>promoter region. The association of c-Myc with the <it>BRCA1 </it>promoter <it>in vivo </it>was tested by a chromatin immunoprecipitation assay. We investigated the function of the c-Myc binding site in the <it>BRCA1 </it>promoter region by a promoter assay with nucleotide substitutions in the putative E boxes. BRCA1-dependent DNA repair activities were measured by a GFP-reporter assay.</p> <p>Results</p> <p>Depletion of c-Myc was found to be correlated with reduced expression levels of <it>BRCA1 </it>mRNA and BRCA1 protein. Depletion of c-Myc decreased <it>BRCA1 </it>promoter activity, while ectopically expressed c-Myc increased <it>BRCA1 </it>promoter activity. In the distal <it>BRCA1 </it>promoter, DNA sequence analysis revealed two tandem clusters with high similarity, and each cluster contained a possible c-Myc binding site. c-Myc bound to these regions <it>in vivo</it>. Nucleotide substitutions in the c-Myc binding sites in these regions abrogated c-Myc-dependent promoter activation. Furthermore, breast cancer cells with reduced BRCA1 expression due to depletion of c-Myc exhibited impaired DNA repair activity.</p> <p>Conclusions</p> <p>The distal <it>BRCA1 </it>promoter region is associated with c-Myc and contributes to <it>BRCA1 </it>gene activation.</p>