1: J Biol Chem. 2003 May 9;278(19):17263-8. Epub 2003 Feb 28. 

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

Moore ML, Park EA, McMillin JB.

Department of Pathology and Laboratory Medicine, The University of Texas Medical
School at Houston, UT-Houston Health Science Center, The Texas Medical Center,
Houston, Texas 77030, USA.

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.

PMID: 12611894 [PubMed - indexed for MEDLINE]


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