Transcriptional Regulation of BRCA1
Abstract
Characterization of the cis and trans regulatory factors involved in BRCA1 transcription, was performed. The previously identified positive regulatory region (PRR), was narrowed to 37 bases by deletion mutations. The region consisted of a Polypyrimidine/Polypurine (py/Pu) motif and a CREB like site. The 37 base pair (bp) region was sufficient to direct transcription. Introduction of point mutations impaired BRCA1 transcription. As this region (specifically Py/Pu) was also responsive to estrogen (reported in the previous summary), we biochemically purified the factors which bind it. These factors were identified by peptide mass fingerprinting analysis as subunits of Replication Protein A. The binding of RPA was verified by supershift assays with monoclonal antibodies. Overall the studies indicate that estrogen responsive site within the BRCA1 promoter binds Replication factors. This also suggests that estrogen signaling to BRCA1 promoter maybe mediated by RPA. Aberrant estrogen signaling and/or abnormal functioning of the RPA complex may compromise BRCA1 transcription and contribute to the observed suppression of BRCA1 mRNA in sporadic breast cancers.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2001
- Accession Number
- ADA398226
Entities
People
- Carlo M. Croce
- Sanjay Thakur
Organizations
- Thomas Jefferson University