Brca1 expression is regulated by a bidirectional promoter that is shared by the Nbr1 gene in mouse.
The lack of functionally disrupting mutations of BRCA1 in sporadic breast tumours has suggested that other mechanisms, including dysregulation of gene expression, might be important in tumour development. We have analysed the control of expression of murine Brca1 and the adjacent gene, Nbr1, which lie head-to-head and are separated by less than 300 bp. Our results show that the expression of these two genes is under complex regulation, through a bidirectional promoter. Brca1 expression is driven by this single promoter, whereas Nbr1 expression is driven by this and one additional promoter, which generate two distinct transcripts, differing by the alternate use of the first exons. By comparison of mRNA transcription in adult murine tissues and also in the mammary gland during pregnancy and lactation, we show that Brca1 and Nbr1 expression is coordinately regulated in a spatial and temporal manner to produce quite different patterns of expression, even from the same promoter. The analysis of the murine and human syntenic region and its control has important implications for the regulation of human and murine BRCA1/NBR1 expression and the interpretation of animal models of disease.
Whitehouse
Caroline
C
Department of Medical and Molecular Genetics, Guy's, King's, and St. Thomas' School of Medicine, Guy's Hospital, 8th Floor, Guy's Tower, London SE1 9RT, UK. caroline.whitehouse@kcl.ac.uk
Chambers
Julie
J
Catteau
Aurélie
A
Solomon
Ellen
E
D016475:3T3 Cells; D000818:Animals; D019313:BRCA1 Protein / Q000235:genetics*; D045744:Cell Line, Tumor; D021901:DNA, Intergenic / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007774:Lactation / Q000502:physiology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D008321:Mammary Glands, Animal / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011401:Promoter Regions, Genetic / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection
D019313:BRCA1 Protein; D021901:DNA, Intergenic; D047908:Intracellular Signaling Peptides and Proteins; C549756:NBR1 protein, human; C486326:Nbr1 protein, mouse; D020033:Protein Isoforms; D011506:Proteins; D011993:Recombinant Fusion Proteins; D008156:Luciferases