Bigenomic transcriptional regulation of all thirteen cytochrome c oxidase subunit genes by specificity protein 1. Open Biol 2013 Mar 20;3(3):120176
Date
03/22/2013Pubmed ID
23516108Pubmed Central ID
PMC3718336DOI
10.1098/rsob.120176Scopus ID
2-s2.0-84877754276 (requires institutional sign-in at Scopus site) 17 CitationsAbstract
Cytochrome c oxidase (COX) is one of only four known bigenomic proteins, with three mitochondria-encoded subunits and 10 nucleus-encoded ones derived from nine different chromosomes. The mechanism of regulating this multi-subunit, bigenomic enzyme is not fully understood. We hypothesize that specificity protein 1 (Sp1) functionally regulates the 10 nucleus-encoded COX subunit genes directly and the three mitochondrial COX subunit genes indirectly by regulating mitochondrial transcription factors A and B (TFAM, TFB1M and TFB2M) in neurons. By means of in silico analysis, electrophoretic mobility shift and supershift assays, chromatin immunoprecipitation, RNA interference and over-expression experiments, the present study documents that Sp1 is a critical regulator of all 13 COX subunit genes in neurons. This regulation is intimately associated with neuronal activity. Silencing of Sp1 prevented the upregulation of all COX subunits by KCl, and over-expressing Sp1 rescued all COX subunits from being downregulated by tetrodotoxin. Thus, Sp1 and our previously described nuclear respiratory factors 1 and 2 are the three key regulators of all 13 COX subunit genes in neurons. The binding sites for Sp1 on all 10 nucleus-encoded COX subunits, TFAM, TFB1M and TFB2M are highly conserved among mice, rats and humans.
Author List
Dhar SS, Johar K, Wong-Riley MTMESH terms used to index this publication - Major topics in bold
AnimalsBase Sequence
Binding Sites
Cell Nucleus
Down-Regulation
Electron Transport Complex IV
Electrophoretic Mobility Shift Assay
Humans
Mice
Mitochondria
Neurons
Potassium Chloride
Promoter Regions, Genetic
Protein Subunits
RNA Interference
RNA, Small Interfering
Rats
Sp1 Transcription Factor
Tetrodotoxin
Transcription Factors
Transcription, Genetic
Up-Regulation
