BRCA1 can stimulate gene transcription by a unique mechanism.
Most familial breast and ovarian cancers have been linked to mutations in the BRCA1 gene. BRCA1 has been shown to affect gene transcription but how it does so remains elusive. Here we show that BRCA1 can stimulate transcription without the requirement for a DNA-tethering function in mammalian and yeast cells. Furthermore, the BRCA1 C-terminal region can stimulate transcription of the p53-responsive promoter, MDM2. Unlike many enhancer-specific activators, non-tethered BRCA1 does not require a functional TATA element to stimulate transcription. Our results suggest that BRCA1 can enhance transcription by a function additional to recruiting the transcriptional machinery to a targeted gene.
Centre de Recherche sur les Mécanismes d'Expression Génétique, Départment de Biologie, Université de Sherbrooke, Québec, Canada.
G
G
Nadeau
N
N
Boufaied
A
A
Moisan
K M
KM
Lemieux
C
C
Cayanan
A N
AN
Monteiro
L
L
Gaudreau
D019313:BRCA1 Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2; D011993:Recombinant Fusion Proteins; D016385:TATA Box / Q000235:genetics; D035181:TATA-Box Binding Protein; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D015003:Yeasts / Q000235:genetics
D019313:BRCA1 Protein; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D035181:TATA-Box Binding Protein; D014157:Transcription Factors; D004247:DNA; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2