Direct stimulation of transcription initiation by BRCA1 requires both its amino and carboxyl termini

Published experiments suggest that BRCA1 interaction with RNAPII and regulation of a number of target genes may be central to its role as a tumor suppressor. Previous in vivo and in vitro work has implicated the carboxyl terminus of BRCA1 in transcriptional stimulation, but the mechanism of action remains unknown, and whether the full- length protein stimulates transcription is controversial. BRCA1 interacts with a number of enhancer- binding transcriptional activators, suggesting that these factors recruit BRCA1 to promoters, where it stimulates RNA synthesis. To investigate whether BRCA1 has intrinsic transcriptional activity, we established a fully purified transcription assay. We demonstrate here that BRCA1 stimulates transcription initiation across a range of promoters. Both the amino and carboxyl termini of BRCA1 are required for this activity, but the BRCA1- binding partner, BARD1, is not. Our data support a model whereby BRCA1 stabilizes productive preinitiation complexes and thus stimulates transcription.