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. 2003 May 9;278(19):17263-8.
doi: 10.1074/jbc.M210486200. Epub 2003 Feb 28.

Upstream stimulatory factor represses the induction of carnitine palmitoyltransferase-Ibeta expression by PGC-1

Meredith L Moore  1 , Edwards A Park, Jeanie B McMillin
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Free article

Upstream stimulatory factor represses the induction of carnitine palmitoyltransferase-Ibeta expression by PGC-1

Meredith L Moore et al. J Biol Chem. .
Free article

Abstract

Transcriptional regulation of carnitine palmitoyltransferase-1beta (CPT-1beta) is coordinated with contractile gene expression through cardiac-enriched transcription factors, GATA4 and SRF. Metabolic modulation of CPT-1beta promoter activity has been described with the stimulation of gene expression by oleate that is mediated through the peroxisome proliferator-activated receptor (PPAR) pathway. The coactivator, peroxisomal proliferator-activated receptor gamma coactivator (PGC-1), enhances gene expression through interactions with nuclear hormone receptors and the myocyte enhancer factor 2 (MEF2) family. PGC-1 and MEF2A synergistically activate CPT-1beta promoter activity. This stimulation is enhanced by mutation of the E-box sequences that flank the MEF2A binding site. These elements bind the upstream stimulatory factors (USF1 and USF2), which activate transcription in CV-1 fibroblasts. However, overexpression of the USF proteins in myocytes depresses CPT-1beta activity and significantly reduces MEF2A and PGC-1 synergy. Co-immunoprecipitation studies demonstrate that PGC-1 and USF2 proteins can physically interact. Our studies demonstrate that PGC-1 stimulates CPT-1beta gene expression through MEF2A. USF proteins have a novel role in repressing the expression of the CPT-1beta gene and modulating the induction by the coactivator, PGC-1.

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