Cytochrome c oxidase is the multisubunit enzyme complex of the mitochondrial inner membrane which transfers electrons from cytochrome c to molecular oxygen and conserves energy as a proton gradient. Characterization of the human gene for the largest nuclear-encoded subunit (subunit IV) of cytochrome oxidase (COX4) led to the identification of a closely linked expressed gene of unknown function. COX4-associated locus (COX4AL) is linked in a head-to-head arrangement with COX4 and thus the intergenic region (250-bp) likely functions as a bidirectional promoter.
The first aim of this project is to determine a possible function of COX4AL by tracking the subcellular location of the 24-kDa encoded protein via immunofluorescence and by determining its association with other cellular proteins using genetic and biochemical approaches. Bidirectional promoters usually encode proteins of similar or related function; thus the specific hypothesis that COX4AL, like COX4, encodes a mitochondrial protein will be tested.
A second aim i s to ascertain whether the COX4/COX4AL intergenic region functions as a bidirectional promoter. Genetic analysis of transfected promoter-reporter gene constructs in human cells will be used to identify promoter elements essential to the expression of each gene. Third, conserved promoter elements in COX4/COX4AL genes will be used to scan the promoters of other coordinately controlled mammalian genes, including those for other nuclear-encoded cytochrome oxidase subunits and bidirectionally controlled genes, to identify new factors that regulate gene expression or to establish new patterns of control used by well-characterized factors. The long-term objective is to contribute to the functional database of the human genome for a region of chromosome 16 shown to encode the cytochrome oxidase subunit IV gene. Future progress in understanding the molecular bases for human disorders depends on having a complete catalog of the functions of human genes and intergenic regions as a """"""""roadmap"""""""" through long stretches of sequence data.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
1R15GM061369-01
Application #
2881158
Study Section
Special Emphasis Panel (ZRG1-GEN (01))
Program Officer
Tompkins, Laurie
Project Start
1999-09-01
Project End
2003-08-31
Budget Start
1999-09-01
Budget End
2003-08-31
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
College at Oneonta
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
City
Albany
State
NY
Country
United States
Zip Code
12201