Control of Human Muscle-type Carnitine Palmitoyltransferase I Gene Transcription by Peroxisome Proliferator-activated Receptor

• Published in: The Journal of biological chemistry 1998-04, Vol.273 (15), p.8560-8563
• Main Authors: Mascaró, Cristina, Acosta, Elena, Ortiz, José A., Marrero, Pedro F., Hegardt, Fausto G., Haro, Diego
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Carnitine O-Palmitoyltransferase - biosynthesis; Carnitine O-Palmitoyltransferase - genetics; Cell Line; Chloramphenicol O-Acetyltransferase - biosynthesis; Consensus Sequence; Exons; Gene Expression Regulation, Enzymologic; Genes, Reporter; Humans; Isoenzymes - biosynthesis; Mice; Muscle, Skeletal - enzymology; Promoter Regions, Genetic; Receptors, Cytoplasmic and Nuclear - biosynthesis; Receptors, Cytoplasmic and Nuclear - metabolism; Recombinant Fusion Proteins - biosynthesis; Regulatory Sequences, Nucleic Acid; Sequence Alignment; Transcription Factors - biosynthesis; Transcription Factors - metabolism; Transcription, Genetic - physiology; Transfection
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.273.15.8560

The expression of several genes involved in intra- and extracellular lipid metabolism, notably those involved in peroxisomal and mitochondrial β-oxidation, is mediated by ligand-activated receptors, collectively referred to as peroxisome proliferator-activated receptors (PPARs). To gain more insight into the control of expression of carnitine palmitoyltransferase (CPT) genes, which are regulated by fatty acids, we have examined the transcriptional regulation of the human MCPT I gene. We have cloned by polymerase chain reaction the 5′-flanking region of this gene and demonstrated its transcriptional activity by transfection experiments with the CAT gene as a reporter. We have also shown that this is a target gene for the action of PPARs, and we have localized a PPAR responsive element upstream of the first exon. These results show that PPAR regulates the entry of fatty acids into the mitochondria, which is a crucial step in their metabolism, especially in tissues like heart, skeletal muscle and brown adipose tissue in which fatty acids are a major source of energy.