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

Meredith L. Moore, Edwards Park, Jeanie B. McMillin

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Transcriptional regulation of carnitine palmitoyltransferase-1β (CPT-1β) is coordinated with contractile gene expression through cardiac-enriched transcription factors, GATA4 and SRF. Metabolic modulation of CPT-1β 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 γ 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-1β 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-Iβ 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-1β gene expression through MEF2A. USF proteins have a novel role in repressing the expression of the CPT-1β gene and modulating the induction by the coactivator, PGC-1.

Original languageEnglish (US)
Pages (from-to)17263-17268
Number of pages6
JournalJournal of Biological Chemistry
Volume278
Issue number19
DOIs
StatePublished - May 9 2003

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Upstream Stimulatory Factors
Carnitine O-Palmitoyltransferase
Gene expression
Gene Expression
MEF2 Transcription Factors
E-Box Elements
Serum Response Factor
Peroxisome Proliferator-Activated Receptors
Proteins
Transcription
Fibroblasts
Oleic Acid
Cytoplasmic and Nuclear Receptors
Immunoprecipitation
Muscle Cells
Genes
Binding Sites
Modulation
Mutation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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Upstream stimulatory factor represses the induction of carnitine palmitoyltransferase-Iβ expression by PGC-1. / Moore, Meredith L.; Park, Edwards; McMillin, Jeanie B.

In: Journal of Biological Chemistry, Vol. 278, No. 19, 09.05.2003, p. 17263-17268.

Research output: Contribution to journalArticle

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