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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
33
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pubmed:dateCreated |
1995-9-18
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pubmed:abstractText |
The long-chain acyl-coenzyme A synthetase (ACS) gene gives rise to three transcripts containing different first exons preceded by specific regulatory regions A, B, and C. Exon-specific oligonucleotide hybridization indicated that only A-ACS mRNA is expressed in rat liver. Fibrate administration induced liver C-ACS strongly and A-ACS mRNA to a lesser extent. B-ACS mRNA remained undetectable. In primary rat hepatocytes and Fa-32 hepatoma cells C-ACS mRNA increased after treatment with fenofibric acid, alpha-bromopalmitate, tetradecylthioacetic acid, or alpha-linolenic acid. Nuclear run-on experiments indicated that fenofibric acid and alpha-bromopalmitate act at the transcriptional level. Transient transfections showed a 3.4-, 2.3-, and 2.2-fold induction of C-ACS promoter activity after fenofibric acid, alpha-bromopalmitate, and tetradecylthioacetic acid, respectively. Unilateral deletion and site-directed mutagenesis identified a peroxisome proliferator activator receptor (PPAR)-responsive element (PPRE) mediating the responsiveness to fibrates and fatty acids. This ACS PPRE contains three imperfect half sites spaced by 1 and 3 oligonucleotides and binds PPAR.retinoid X receptor heterodimers in gel retardation assays. In conclusion, the regulation of C-ACS mRNA expression by fibrates and fatty acids is mediated by PPAR.retinoid X receptor heterodimers interacting through a PPRE in the C-ACS promoters. PPAR therefore occupies a key position in the transcriptional control of a pivotal enzyme controlling the channeling of fatty acids into various metabolic pathways.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Coenzyme A Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/FAA2 protein, S cerevisiae,
http://linkedlifedata.com/resource/pubmed/chemical/Fatty Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Fenofibrate,
http://linkedlifedata.com/resource/pubmed/chemical/Oligodeoxyribonucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/Propionates,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Saccharomyces cerevisiae Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/long-chain-fatty-acid-CoA ligase
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
18
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pubmed:volume |
270
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
19269-76
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:7642600-Animals,
pubmed-meshheading:7642600-Base Sequence,
pubmed-meshheading:7642600-Cells, Cultured,
pubmed-meshheading:7642600-Coenzyme A Ligases,
pubmed-meshheading:7642600-Exons,
pubmed-meshheading:7642600-Fatty Acids,
pubmed-meshheading:7642600-Fenofibrate,
pubmed-meshheading:7642600-Liver,
pubmed-meshheading:7642600-Male,
pubmed-meshheading:7642600-Microbodies,
pubmed-meshheading:7642600-Molecular Sequence Data,
pubmed-meshheading:7642600-Oligodeoxyribonucleotides,
pubmed-meshheading:7642600-Promoter Regions, Genetic,
pubmed-meshheading:7642600-Propionates,
pubmed-meshheading:7642600-Protein Binding,
pubmed-meshheading:7642600-RNA, Messenger,
pubmed-meshheading:7642600-Rats,
pubmed-meshheading:7642600-Rats, Sprague-Dawley,
pubmed-meshheading:7642600-Rats, Wistar,
pubmed-meshheading:7642600-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:7642600-Repressor Proteins,
pubmed-meshheading:7642600-Saccharomyces cerevisiae Proteins,
pubmed-meshheading:7642600-Transcription, Genetic,
pubmed-meshheading:7642600-Transcription Factors,
pubmed-meshheading:7642600-Tumor Cells, Cultured
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pubmed:year |
1995
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pubmed:articleTitle |
Induction of the acyl-coenzyme A synthetase gene by fibrates and fatty acids is mediated by a peroxisome proliferator response element in the C promoter.
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pubmed:affiliation |
Laboratoire de Biologie des Régulations chez les Eucaryotes, Institut Pasteur, Lille, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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