PPAR-RXR heterodimer activates a peroxisome proliferator response element upstream of the bifunctional enzyme gene.
A DNA sequence that confers a response to a class of rodent hepatocarcinogens termed peroxisome proliferators has been identified 2947bp upstream of the rat peroxisomal bifunctional enzyme gene. Two members of the steroid hormone receptor family, termed the peroxisome proliferator activated receptor (PPAR alpha) and the retinoid X receptor (RXR alpha), co-operate to bind specifically to this sequence. Importantly, this response element (PPRE) is similar to that identified upstream of other peroxisome proliferator responsive genes such as those encoding acyl CoA oxidase and cytochrome P450 IVA6. These data therefore provide further evidence that PPAR alpha plays an important role in mediating the action of peroxisome proliferators.
ZENECA Central Toxicology Laboratory, Macclesfield, Cheshire, UK.
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D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004746:Enoyl-CoA Hydratase / Q000235:genetics*; D007535:Isomerases / Q000235:genetics*; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000235:genetics*; D009687:Nuclear Proteins / Q000378:metabolism*; D009841:Oligonucleotides; D063994:Peroxisomal Bifunctional Enzyme; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D012045:Regulatory Sequences, Nucleic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000378:metabolism*
D009097:Multienzyme Complexes; D009687:Nuclear Proteins; D009841:Oligonucleotides; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D004247:DNA; D015094:3-Hydroxyacyl CoA Dehydrogenases; D004746:Enoyl-CoA Hydratase; D063994:Peroxisomal Bifunctional Enzyme; D007535:Isomerases