Mammalian cytochrome c oxidase (COX) consists of 13 subunits: three encoded in mitochondrial DNA and 10 in nuclear DNA. Long- term goals are to understand the regulation of this critically important enzyme complex through analysis of the genetic regulatory sequences controlling expression of COX nuclear genes. Short term goals include defining the cis-regulatory sequence elements (cis- elements) in the promoters of two COX genes: human COX5B (for a ubiquitous subunit VB), and bovine COX8H (for subunit VIII-heart). They will: (1) identify by DNA sequencing those cis-elements in the promoter of the COX5B gene known to be important for transcriptional control of other genes; (2) identify unique cis- elements important for transcriptional control of respiratory genes by functional analysis of the COX5B promoter through a) analysis of DNAseI hypersensitive sites, b) gene fusion experiments, and C) transient expression studies; (3) clone and sequence the promoter of the bovine COX8H gene to identify unique cis-elements important for tissue-specific expression. These studies on the cis- regulatory sequence elements controlling expression of nuclear genes for this unique enzyme complex will contribute to our understanding of the genetic regulatory signals involved in mitochondrial biogenesis and in tissue=specific expression of this important enzyme complex.*** //
