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Cited by 395

The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.

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

Open access
Schoonjans, Kristina, Watanabe, Mitsuhiro, Suzuki, Hiroyuki, Mahfoudi, Abderrahim, Krey, Grigorios, Wahli, Walter, Grimaldi, Paul, Staels, Bart, Yamamoto, Tokuo, Auwerx, Johan·1995·Journal of Biological Chemistry

Abstract

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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Crossref · 10.1074/jbc.270.33.19269

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Metadata

Authors
Schoonjans, K., Watanabe, M., Suzuki, H., Mahfoudi, A., Krey, G., Wahli, W., Grimaldi, P., Staels, B., Yamamoto, T., & Auwerx, J.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1995-08
Volume
270
Issue
33
Pages
19269-19276
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2037094605
Cited by
395
References
3
FWCI
5.21
Type
journal article
Language
en
Open access
hybrid

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