Control of human carnitine palmitoyltransferase II gene transcription by peroxisome proliferator-activated receptor through a partially conserved peroxisome proliferator-responsive element.
The expression of several genes involved in fatty acid metabolism is regulated by peroxisome proliferator-activated receptors (PPARs). To gain more insight into the control of carnitine palmitoyltransferase (CPT) gene expression, we examined the transcriptional regulation of the human CPT II gene. We show that the 5'-flanking region of this gene is transcriptionally active and binds PPARalpha in vivo in a chromatin immunoprecipitation assay. In addition, we characterized the peroxisome proliferator-responsive element (PPRE) in the proximal promoter of the CPT II gene, which appears to be a novel PPRE. The sequence of this PPRE contains one half-site which is a perfect consensus sequence (TGACCT) but no clearly recognizable second half-site (CAGCAC); this part of the sequence contains only one match to the consensus, which seems to be irrelevant for the binding of PPARalpha. As expected, other members of the nuclear receptor superfamily also bind to this element and repress the activation mediated by PPARalpha, thus showing that the interplay between several nuclear receptors may regulate the entry of fatty acids into the mitochondria, a crucial step in their metabolism.
Barrero
María J
MJ
Departament de Bioquímica i Biologia Molecular, Facultat de Farmàcia, Avda. Diagonal, 643, E-08028 Barcelona, Spain.
Camarero
Nuria
N
Marrero
Pedro F
PF
Haro
Diego
D
D001483:Base Sequence; D001665:Binding Sites; D051838:COUP Transcription Factor I; D006528:Carcinoma, Hepatocellular / Q000235:genetics; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics* / Q000378:metabolism; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics; D011401:Promoter Regions, Genetic; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D020218:Response Elements; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D000097983:ERRalpha Estrogen-Related Receptor
D051838:COUP Transcription Factor I; D002334:Carnitine O-Palmitoyltransferase; D004268:DNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; D014157:Transcription Factors; D000097983:ERRalpha Estrogen-Related Receptor; C497589:NR2F1 protein, human