Expression of the rat liver carnitine palmitoyltransferase I (CPT-Iα) gene is regulated by Sp1 and nuclear factor Y: chromosomal localization and promoter characterization

• Published in: Biochemical journal Vol. 340; no. 2; pp. 425 - 432
• Main Authors: STEFFEN, Michelle L., HARRISON, Wilbur R., ELDER, Frederick F. B., COOK, George A., PARK, Edwards A.
• Format: Journal Article
• Language: English
• Published: 01.06.1999
• ISSN: 0264-6021; 1470-8728
• DOI: 10.1042/bj3400425

Carnitine palmitoyltransferase (CPT)-I catalyses the transfer of long-chain fatty acids from CoA to carnitine for translocation across the mitochondrial inner membrane. Expression of the ‘liver’ isoform of the CPT-I gene (CPT-Iα) is subject to developmental, hormonal and tissue-specific regulation. To understand the basis for control of CPT-Iα gene expression, we have characterized the proximal promoter of the CPT-Iα gene. Here, we report the sequence of 6839 base pairs of the promoter and the localization of the rat CPT-Iα gene to region q43 on chromosome 1. Our studies show that the first 200 base pairs of the promoter are sufficient to drive transcription of the CPT-Iα gene. Within this region are two sites that bind both Sp1 and Sp3 transcription factors. In addition, nuclear factor Y (NF-Y) binds the proximal promoter. Mutation at the Sp1 or NF-Y sites severely decreases transcription from the CPT-Iα promoter. Other protein binding sites were identified within the first 200 base pairs of the promoter by DNase I footprinting, and these elements contribute to CPT-Iα gene expression. Our studies demonstrate that CPT-Iα is a TATA-less gene which utilizes NF-Y and Sp proteins to drive basal expression.