Functional interaction of regulatory factors with the Pgc-1alpha promoter in response to exercise by in vivo imaging.
Real-time optical bioluminescence imaging is a powerful tool for studies of gene regulation in living animals. To elucidate exercise-induced signaling/transcriptional control of the peroxisome proliferator-activated receptor-gamma coactivator-1alpha (Pgc-1alpha) gene in skeletal muscle, we combined this technology with electric pulse-mediated gene transfer to cotransfect the Pgc-1alpha reporter gene with plasmid DNA encoding mutant/deletion forms of putative regulatory factors and, thereby, assess the responsiveness of the promoter to skeletal muscle contraction. We show that each of the myocyte enhancer factor 2 sites on the Pgc-1alpha promoter is required for contractile activity-induced Pgc-1alpha transcription. The responsiveness of the Pgc-1alpha promoter to contractile activity could be completely blocked by overexpression of the dominant-negative form of activating transcription factor 2 (ATF2), the signaling-resistant form of histone deacetylase (HDAC) 5 (HDAC5), or protein kinase D (PKD), but not by HDAC4. These findings provide in vivo evidence for functional interactions between PKD/HDAC5 and ATF2 regulatory factors and the Pgc-1alpha gene in adult skeletal muscle.
Akimoto
Takayuki
T
Department of Medicine, Duke University Medical Center, Durham, NC 27704, USA.
Li
Ping
P
Yan
Zhen
Z
D051698:Activating Transcription Factor 2 / Q000378:metabolism; D000818:Animals; D005786:Gene Expression Regulation; D006655:Histone Deacetylases / Q000378:metabolism; D008163:Luminescent Measurements; D064326:MEF2 Transcription Factors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000502:physiology*; D018006:Myogenic Regulatory Factors / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010805:Physical Conditioning, Animal / Q000502:physiology*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors
D051698:Activating Transcription Factor 2; C497106:Atf2 protein, mouse; D064326:MEF2 Transcription Factors; D018006:Myogenic Regulatory Factors; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; C089212:protein kinase D; D011493:Protein Kinase C; C498618:Hdac5 protein, mouse; D006655:Histone Deacetylases