TY - JOUR
T1 - Functional interaction of regulatory factors with the Pgc-1α promoter in response to exercise by in vivo imaging
AU - Akimoto, Takayuki
AU - Li, Ping
AU - Yan, Zhen
N1 - Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2008/7
Y1 - 2008/7
N2 - 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-γ coactivator-1α (Pgc-1α) gene in skeletal muscle, we combined this technology with electric pulse-mediated gene transfer to cotransfect the Pgc-1α 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-1α promoter is required for contractile activity-induced Pgc-1α transcription. The responsiveness of the Pgc-1α 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-1α gene in adult skeletal muscle.
AB - 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-γ coactivator-1α (Pgc-1α) gene in skeletal muscle, we combined this technology with electric pulse-mediated gene transfer to cotransfect the Pgc-1α 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-1α promoter is required for contractile activity-induced Pgc-1α transcription. The responsiveness of the Pgc-1α 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-1α gene in adult skeletal muscle.
KW - Electric pulse-mediated gene transfer
KW - Optical biolunminescence imaging
KW - Reporter gene
KW - Signal transduction
KW - Transcriptional control
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U2 - 10.1152/ajpcell.00104.2008
DO - 10.1152/ajpcell.00104.2008
M3 - Article
C2 - 18434626
AN - SCOPUS:52749095883
VL - 295
SP - C288-C292
JO - American Journal of Physiology - Cell Physiology
JF - American Journal of Physiology - Cell Physiology
SN - 0363-6143
IS - 1
ER -