Isolation and Characterisation of the NBR2 Gene Which Lies Head to Head with the Human BRCA1 Gene

• Published in: Human molecular genetics Vol. 6; no. 7; pp. 1057 - 1062
• Main Authors: Xu, Chun-Fang, Brown, Melissa A., Nicolai, Hans, Chambers, Julie A., Griffiths, Beatrice L., Solomon, Ellen
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-07-1997
• Subjects: Amino Acid Sequence; Animals; Biological and medical sciences; Blotting, Northern; BRCA1 Protein - genetics; Breast Neoplasms - genetics; Chromosome Mapping; Cloning, Molecular; Conserved Sequence; DNA Mutational Analysis; DNA, Complementary; Evolution, Molecular; Exons; Female; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; Genes. Genome; Humans; Intracellular Signaling Peptides and Proteins; Introns; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Neoplasm Proteins; Ovarian Neoplasms - genetics; Primates; Proteins - genetics; Proteins - metabolism; Pseudogenes; Transcription Factors; Human; Regulation(control); Nucleotide sequence; Transcription promoter; Critical region; Tissue specificity; Homology; Gene organization; Gene expression; Tumor suppressor gene
• ISSN: 0964-6906; 1460-2083; 1460-2083
• DOI: 10.1093/hmg/6.7.1057

To study the regulation of BRCA1 gene expression and the potential importance of dysregulation of this gene in breast and ovarian cancer, we have examined the 5′ region of the human BRCA1 gene in detail. We have identified a new gene, NBR2, which is partially related to the NBR1 gene (formerly known as 1A1-3B and mapping directly adjacent to the pseudo-BRCA1 gene) and which lies head to head with the BRCA1 gene. The physical distance between the transcription start sites of the NBR2 and BRCA1 genes is 218 bp, suggesting that regulation of the expression of both genes may be co-ordinated through a bi-directional promoter. The NBR2 gene contains five exons spanning a genomic region of 30 kb between the BRCA1 and pseudo-BRCA1 genes. Northern analysis showed that theNBR2 gene is expressed in all the tissues examined. The NBR2 cDNA contains an open reading frame of 112 amino acids and is predicted to encode a protein of ∼12 kDa. Single-strand conformation polymorphism (SSCP) analysis of the NBR2 gene failed to identify any mutations in either breast or ovarian cancer, suggesting that if the NBR2 gene is involved in the development of these cancers, other mechanisms for tumorigenesis may exist. Hybridisation of NBR2 probes to zoo blots showed that the NBR2 gene is present in human and other primates. No hybridisation to DNA from other species was observed, suggesting that genomic elements controlling BRCA1 expression may differ between species.