Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
17
pubmed:dateCreated
2004-5-4
pubmed:abstractText
Recent studies have shown that genes involved in oxidative phosphorylation (OXPHOS) exhibit reduced expression in skeletal muscle of diabetic and prediabetic humans. Moreover, these changes may be mediated by the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha). By combining PGC-1alpha-induced genome-wide transcriptional profiles with a computational strategy to detect cis-regulatory motifs, we identified estrogen-related receptor alpha (Erralpha) and GA repeat-binding protein alpha as key transcription factors regulating the OXPHOS pathway. Interestingly, the genes encoding these two transcription factors are themselves PGC-1alpha-inducible and contain variants of both motifs near their promoters. Cellular assays confirmed that Erralpha and GA-binding protein a partner with PGC-1alpha in muscle to form a double-positive-feedback loop that drives the expression of many OXPHOS genes. By using a synthetic inhibitor of Erralpha, we demonstrated its key role in PGC-1alpha-mediated effects on gene regulation and cellular respiration. These results illustrate the dissection of gene regulatory networks in a complex mammalian system, elucidate the mechanism of PGC-1alpha action in the OXPHOS pathway, and suggest that Erralpha agonists may ameliorate insulin-resistance in individuals with type 2 diabetes mellitus.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/15100410, http://linkedlifedata.com/resource/pubmed/commentcorrection/15100410-10391217, http://linkedlifedata.com/resource/pubmed/commentcorrection/15100410-10412986, http://linkedlifedata.com/resource/pubmed/commentcorrection/15100410-10713087, http://linkedlifedata.com/resource/pubmed/commentcorrection/15100410-11167019, http://linkedlifedata.com/resource/pubmed/commentcorrection/15100410-11175784, http://linkedlifedata.com/resource/pubmed/commentcorrection/15100410-11274399, http://linkedlifedata.com/resource/pubmed/commentcorrection/15100410-11872831, http://linkedlifedata.com/resource/pubmed/commentcorrection/15100410-11943463, http://linkedlifedata.com/resource/pubmed/commentcorrection/15100410-12031981, http://linkedlifedata.com/resource/pubmed/commentcorrection/15100410-12101404, http://linkedlifedata.com/resource/pubmed/commentcorrection/15100410-12181319, http://linkedlifedata.com/resource/pubmed/commentcorrection/15100410-12181572, http://linkedlifedata.com/resource/pubmed/commentcorrection/15100410-12351431, http://linkedlifedata.com/resource/pubmed/commentcorrection/15100410-12522104, http://linkedlifedata.com/resource/pubmed/commentcorrection/15100410-12529312, http://linkedlifedata.com/resource/pubmed/commentcorrection/15100410-12588810, http://linkedlifedata.com/resource/pubmed/commentcorrection/15100410-12626739, http://linkedlifedata.com/resource/pubmed/commentcorrection/15100410-12734177, http://linkedlifedata.com/resource/pubmed/commentcorrection/15100410-12748633, http://linkedlifedata.com/resource/pubmed/commentcorrection/15100410-12750520, http://linkedlifedata.com/resource/pubmed/commentcorrection/15100410-12764228, http://linkedlifedata.com/resource/pubmed/commentcorrection/15100410-12808457, http://linkedlifedata.com/resource/pubmed/commentcorrection/15100410-12824349, http://linkedlifedata.com/resource/pubmed/commentcorrection/15100410-12832613, http://linkedlifedata.com/resource/pubmed/commentcorrection/15100410-12958173, http://linkedlifedata.com/resource/pubmed/commentcorrection/15100410-12963016, http://linkedlifedata.com/resource/pubmed/commentcorrection/15100410-14530391, http://linkedlifedata.com/resource/pubmed/commentcorrection/15100410-14585956, http://linkedlifedata.com/resource/pubmed/commentcorrection/15100410-14651853, http://linkedlifedata.com/resource/pubmed/commentcorrection/15100410-8108407, http://linkedlifedata.com/resource/pubmed/commentcorrection/15100410-8393666, http://linkedlifedata.com/resource/pubmed/commentcorrection/15100410-9058380, http://linkedlifedata.com/resource/pubmed/commentcorrection/15100410-9271417, http://linkedlifedata.com/resource/pubmed/commentcorrection/15100410-9461436
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0027-8424
pubmed:author
pubmed:issnType
Print
pubmed:day
27
pubmed:volume
101
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6570-5
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed-meshheading:15100410-Animals, pubmed-meshheading:15100410-Base Sequence, pubmed-meshheading:15100410-DNA Primers, pubmed-meshheading:15100410-DNA-Binding Proteins, pubmed-meshheading:15100410-Diabetes Mellitus, Experimental, pubmed-meshheading:15100410-Evolution, Molecular, pubmed-meshheading:15100410-GA-Binding Protein Transcription Factor, pubmed-meshheading:15100410-Gene Expression Regulation, pubmed-meshheading:15100410-Mice, pubmed-meshheading:15100410-Oxidative Phosphorylation, pubmed-meshheading:15100410-Polymerase Chain Reaction, pubmed-meshheading:15100410-Receptors, Cytoplasmic and Nuclear, pubmed-meshheading:15100410-Receptors, Estrogen, pubmed-meshheading:15100410-Trans-Activators, pubmed-meshheading:15100410-Transcription, Genetic, pubmed-meshheading:15100410-Transcription Factors, pubmed-meshheading:15100410-Transfection
pubmed:year
2004
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