Abstract
Peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha), a tissue-specific and inducible transcriptional coactivator for several nuclear receptors, plays a key role in energy metabolism. We report here that PGC-1alpha coactivator activity is potentiated by arginine methylation by protein arginine methyltransferase 1 (PRMT1), another nuclear receptor coactivator. Mutation of three substrate arginines in the C-terminal region of PGC-1alpha abolished the cooperative coactivator function of PGC-1alpha and PRMT1, and compromised the ability of PGC-1alpha to induce endogenous target genes. Finally, endogenous PRMT1 contributes to PGC-1alpha coactivator activity, and to the induction of genes important for mitochondrial biogenesis.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Arginine / chemistry
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Base Sequence
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Cell Line
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DNA, Complementary / genetics
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Gene Expression Regulation
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Heat-Shock Proteins / chemistry
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Heat-Shock Proteins / genetics
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Heat-Shock Proteins / metabolism*
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Humans
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In Vitro Techniques
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Methylation
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Mutagenesis, Site-Directed
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
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Protein Structure, Tertiary
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Protein-Arginine N-Methyltransferases / metabolism
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Transcription Factors / chemistry
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Transcription Factors / genetics
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Transcription Factors / metabolism*
Substances
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DNA, Complementary
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Heat-Shock Proteins
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PPARGC1A protein, human
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
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Recombinant Proteins
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Transcription Factors
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Arginine
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Protein-Arginine N-Methyltransferases