Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 281, Issue 13, Pages 8317-8320Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.C500475200
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Funding
- NCI NIH HHS [CA90281] Funding Source: Medline
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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.
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