Submitted on February 19, 2008
Revised on April 16, 2008
Accepted on April 17, 2008
Functional interaction of regulatory factors with the Pgc-1
promoter in response to exercise by in vivo imaging
Takayuki Akimoto, Ping Li, and Zhen Yan1*
1 Duke University Medical Center
* To whom correspondence should be addressed. E-mail: zhen.yan{at}duke.edu.
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 
coactivator-1
(Pgc-1) gene in skeletal muscle, we combined this technology with electric pulse-mediated gene transfer to co-transfect Pgc-1 reporter gene with plasmid DNA encoding mutant/deletion forms of putative regulatory factors to assess the responsiveness of the promoter to skeletal muscle contraction. We show here that each of the MEF2 sites on the Pgc-1 promoter is required for contractile activity-induced Pgc-1 transcription. The responsiveness of the Pgc-1 promoter to contractile activity could be completely blocked by overexpression of dominant negative form of activating transcription factor 2 (ATF2), signaling-resistant form of histone deacetylase 5 (HDAC5) or protein kinase D (PKD), but not by that of HDAC4. These findings provide in vivo evidence for functional interactions between PKD/HDAC5 and ATF2 regulatory factors and the Pgc-1 gene in adult skeletal muscle.
