c-Myc activates BRCA1 gene expression through distal promoter elements in breast cancer cells.
Bottom Line: Depletion of c-Myc was found to be correlated with reduced expression levels of BRCA1 mRNA and BRCA1 protein.Depletion of c-Myc decreased BRCA1 promoter activity, while ectopically expressed c-Myc increased BRCA1 promoter activity.The distal BRCA1 promoter region is associated with c-Myc and contributes to BRCA1 gene activation.
Affiliation: Center for Clinical Cancer Genetics and Global Health, Department of Medicine, University of Chicago, Chicago, IL, USA.Show MeSH
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Mentions: c-Myc regulatory sites within gene promoter regions, such as the cognate hexanucleotide E box (CACGTG) and non-cognate E boxes have been well documented, but the DNA sequences of c-Myc binding regions could be more degenerate . In order to identify c-Myc interacting elements, we used these E box sequences to search for possible matches in the -1714 to +42 region of the BRCA1 promoter, which is responsive to c-Myc activation. Two nucleotide regions, -1292 to -1286 (E box Y) and -912 to -907 (E box X), were found to be either identical to or with high similarity to E box sequences (Figure 3A). One nucleotide at position 4 of E box X; (-909: G to T) differed from the cognate E box sequence CACGTG, while seven nucleotides of E box Y were identical to the non-cognate E box sequence CACGTTG. An alignment of the putative E boxes and their adjacent regions is shown in Figure 3B. Almost half of the nucleotides (12 to 30) were identical in two DNA clusters, which indicated that these regions could serve as a tandem array that facilitates c-Myc-containing transcription factor binding (Figure 3B).
Affiliation: Center for Clinical Cancer Genetics and Global Health, Department of Medicine, University of Chicago, Chicago, IL, USA.