http://www.jbc.org/cgi/content/abstract/C500475200v1?etoc
Direct stimulation of transcription initiation by BRCA1 requires both its amino and carboxy-termini
Andrew A. Horwitz, Satish Sankaran, and Jeffrey D. Parvin
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 carboxy-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 carboxy-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 pre-initiation complexes and thus stimulates transcription.
