GENOMIC SEQUENCE AND ORGANIZATION OF THE HUMAN GENE FOR CYTOCHROME-C-OXIDASE SUBUNIT (COX7A1) VIIA-M

Cytochrome c oxidase (COX, EC 1.9.3.1), the last component of the mito chondrial electron transfer chain, is built up by 13 polypeptides; 3 o f them are encoded by the mitochondrial genome while the 10 smaller su bunits are encoded by the nuclear genome. Several nuclear-encoded subu nits occur in two different tissue-specific isoforms, a constitutive ' 'L''-form and an ''M''-form specific for skeletal and heart muscle. In this article, we describe the genomic sequence and organization of th e human gene for COX subunit VIIa-M (COX7A1) located on chromosome 19q 13.1 and compare it to its bovine homologue. The coding region of the gene extends over 1.45 kb of genomic sequence, organized in four exons . Intron-exon boundaries are well conserved between cattle and humans. Although it is a gene for a tissue-specific isoform, it has some feat ures of a housekeeping gene: it is located in a CpG island, like its b ovine homologue, and no TATA or CCAAT boxes were found in the 5' flank ing sequence. Southern hybridization of COX7A1 to human genomic DNA re vealed no pseudogenes. Putative binding sites for ubiquitous transcrip tion factors like Spl and specific expression in skeletal as well as i n heart muscle have been found. In contrast to the bovine gene, the hu man gene contains putative binding sites for nuclear respiratory facto r 2 (NRF-2), which is implicated in the activation of other respirator y enzymes. Therefore, the human and the bovine genes, although well co nserved in their coding regions, could differ in the tissue-specific r egulation of gene expression. Knowledge of the gene structure will fac ilitate the analysis of the involvement of subunit VIIa in mitochondri al myopathies and may provide clues to the function of this subunit in a multicomponent enzyme. (C) 1997 Academic Press.