Isolation and characterization of the functional gene encoding bovine cytochrome c oxidase subunit IV

The structure and expression of the gene (COX4) encoding bovine cytochrome c oxidase subunit IV (COX IV) was studied in order to identify conserved DNA sequence elements involved in the control of mammalian nuclear respiratory genes. The functional bovine COX4 gene consists of five exons and four introns and is similar in organization to rat and mouse COX4. The domain encoded by exon 3 is the most highly conserved among the three species, suggesting it may encode a key functional domain of COX IV. Transcription of bovine COX4 begins at multiple sites, as has been seen previously for rat and mouse COX4 and other TATA-less genes. Comparative analysis of bovine, rat and mouse COX4 promoters identified multiple binding sites for the regulatory proteins Sp1 and GABP (NRF-2). The varied arrangements of multiple Sp1 and GABP sites in mammalian COX4 promoters suggests flexibility in the positioning of regulatory factors in controlling COX4 expression.