Faculty Collaboration Database

Is nuclear respiratory factor 2 a master transcriptional coordinator for all ten nuclear-encoded cytochrome c oxidase subunits in neurons? Gene 2005 Oct 24;360(1):65-77

Date

08/30/2005

Pubmed ID

16126350

DOI

10.1016/j.gene.2005.06.015

Scopus ID

2-s2.0-26444545461 (requires institutional sign-in at Scopus site)   94 Citations

Abstract

Cytochrome c oxidase (COX), the terminal enzyme of the mitochondrial electron transport chain, is a multi-subunit, bigenomically encoded inner mitochondrial membrane protein. Of the thirteen subunits, three are encoded in the mitochondrial genome and ten others are encoded in the nuclear genome. Transcriptional coordination of nuclear-encoded COX subunit genes is likely accomplished by transcription factors responding to upstream signals. Previous studies have found that nuclear-encoded COX subunit genes are under the control of specific transcription factors, such as nuclear respiratory factor 2 (NRF-2). However, it is not known if a single transcription factor binds to all ten of COX subunit promoters. In the current study, we identified in silico putative NRF-2 binding sites on all ten nuclear-encoded COX gene promoters in the rat genome. Chromatin immunoprecipitation assay showed that NRF-2 bound in vivo to six of the ten nuclear-encoded COX subunit promoters. Electrophoretic mobility supershift assays demonstrated binding of NRF-2 to the other four subunits, and promoter mutation study confirmed the functionality of these NRF-2 binding sites. Finally, transfection of dominant-negative constructs of NRF-2 proteins caused a significant reduction of COX expression. We conclude that NRF-2 is an important mediator of coordinated regulation of all ten nuclear-encoded COX subunit genes in neurons.

Author List

Ongwijitwat S, Wong-Riley MT

Author

Margaret Wong-Riley PhD, MA Emeritus Professor in the Cell Biology Neurobiology and Anatomy department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Animals, Newborn
Base Sequence
Cells, Cultured
Cerebral Cortex
Chromatin Immunoprecipitation
Electron Transport Complex IV
GA-Binding Protein Transcription Factor
Gene Expression Regulation
Genes, Dominant
Molecular Sequence Data
Neurons
Promoter Regions, Genetic
Protein Binding
Rats
Regulatory Sequences, Nucleic Acid
Transfection