title: Functional interactions of peroxisome proliferator-activated receptor, retinoid-X receptor, and Sp1 in the transcriptional regulation of the acyl-coenzyme-A oxidase promoter.
abstract: Peroxisome proliferator-activated receptor (PPARs) are members of the nuclear receptor superfamily. For transcriptional activation of their target genes, PPARs heterodimerize with the retinoid-X receptor (RXR). The convergence of the PPAR and RXR signaling pathways has been shown to have an important function in lipid metabolism. The promoter of the gene encoding the acyl-coenzyme-A oxidase (ACO), the rate-limiting enzyme in peroxisomal beta-oxidation of fatty acids, is a target site of PPAR action. In this study, we examined the role and the contribution of both cis-and trans-acting factors in the transcriptional regulation of this gene using transient transfections in insect cells. We identified several functional cis-acting elements present in the promoter of the ACO gene and established that PPAR-dependent as well as PPAR-independent mechanisms can activate the ACO promoter in these cells. We show that the PPAR/RXR heterodimer exerts its effect through two response elements within the ACO promoter, in synergy with the transcription factor Sp1 via five Sp1-binding sites. Furthermore, this functional interaction also occurs when Sp1 is co-expressed with PPAR or RXR alone, indicating that activation can occur independently of PPAR/RXR heterodimers.
authors.affiliation: Institut de Biologie Animale, Université de Lausanne, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: Krey
authors.forename: A
authors.initials: A
authors.lastname: Mahfoudi
authors.forename: W
authors.initials: W
authors.lastname: Wahli
mesh_terms: D042962:Acyl-CoA Oxidase; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D016384:Consensus Sequence; D004330:Drosophila; D015971:Gene Expression Regulation, Enzymologic; D017930:Genes, Reporter; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010088:Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid; D047488:Retinoid X Receptors; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D010088:Oxidoreductases; D042962:Acyl-CoA Oxidase