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Biochem Biophys Res Commun. 2009 Apr 17;381(4):537-43. doi: 10.1016/j.bbrc.2009.02.077. Epub 2009 Feb 20.

Identification and characterization of an alternative promoter of the human PGC-1alpha gene.

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1
Department of Internal Medicine, Kobe University Graduate School of Medicine, Chuo-ku, Japan.

Abstract

The transcriptional regulator peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) controls mitochondrial biogenesis and energy homeostasis. Although physical exercise induces PGC-1alpha expression in muscle, the underlying mechanism of this effect has remained incompletely understood. We recently identified a novel muscle-enriched isoform of PGC-1alpha transcript (designated PGC-1alpha-b) that is derived from a previously unidentified first exon. We have now cloned and characterized the human PGC-1alpha-b promoter. The muscle-specific transcription factors MyoD and MRF4 transactivated this promoter through interaction with a proximal E-box motif. Furthermore, either forced expression of Ca(2+)- and calmodulin-dependent protein kinase IV (CaMKIV), calcineurin A, or the p38 mitogen-activated protein kinase (p38 MAPK) kinase MKK6 or the intracellular accumulation of cAMP activated the PGC-1alpha-b promoter in cultured myoblasts through recruitment of cAMP response element (CRE)-binding protein (CREB) to a putative CRE located downstream of the E-box. Our results thus reveal a potential molecular basis for isoform-specific regulation of PGC-1alpha expression in contracting muscle.

PMID:
19233136
DOI:
10.1016/j.bbrc.2009.02.077
[Indexed for MEDLINE]
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