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Originally published In Press as doi:10.1074/jbc.M210486200 on February 28, 2003

J. Biol. Chem., Vol. 278, Issue 19, 17263-17268, May 9, 2003
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Upstream Stimulatory Factor Represses the Induction of Carnitine Palmitoyltransferase-Ibeta Expression by PGC-1*

Meredith L. Moore, Edwards A. ParkDagger , and Jeanie B. McMillin§

From the Department of Pathology and Laboratory Medicine, The University of Texas Medical School at Houston, UT-Houston Health Science Center and the Graduate School of Biomedical Sciences, The Texas Medical Center, Houston, Texas 77030 and the Dagger  Department of Pharmacology, The University of Tennessee, Memphis, Tennessee 38163

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.


* This work was supported by National Institutes of Health Grant RO1 HL38863, the Juvenile Diabetes Research Foundation (JDRF), and the American Heart Association (AHA).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ To whom correspondence should be addressed: Dept. of Pathology and Laboratory Medicine, The University of Texas Medical School at Houston, 6431 Fannin, Houston, TX 77030. Tel.: 713-500-5335; Fax: 703-500-0730; E-mail: Jeanie.B.McMillin@uth.tmc.edu.


Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
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