title: Promoter-specific regulation of PPARGC1A gene expression in human skeletal muscle.
abstract: The goal of this study was to identify unknown transcription start sites of the PPARGC1A (PGC-1α) gene in human skeletal muscle and investigate the promoter-specific regulation of PGC-1α gene expression in human skeletal muscle. Ten amateur endurance-trained athletes performed high- and low-intensity exercise sessions (70  min, 70% or 50% o2max). High-throughput RNA sequencing and exon-exon junction mapping were applied to analyse muscle samples obtained at rest and after exercise. PGC-1α promoter-specific expression and activation of regulators of PGC-1α gene expression (AMPK, p38 MAPK, CaMKII, PKA and CREB1) after exercise were evaluated using qPCR and western blot. Our study has demonstrated that during post-exercise recovery, human skeletal muscle expresses the PGC-1α gene via two promoters only. As previously described, the additional exon 7a that contains a stop codon was found in all samples. Importantly, only minor levels of other splice site variants were found (and not in all samples). Constitutive expression PGC-1α gene occurs via the canonical promoter, independent of exercise intensity and exercise-induced increase of AMPK(Thr172) phosphorylation level. Expression of PGC-1α gene via the alternative promoter is increased of two orders after exercise. This post-exercise expression is highly dependent on the intensity of exercise. There is an apparent association between expression via the alternative promoter and activation of CREB1.
authors: Laboratory of Exercise PhysiologyInstitute of Biomedical Problems, Russian Academy of Sciences, Khoroshevskoye shosse, 76A, Moscow 123007, RussiaFaculty of Fundamental MedicineM.V. Lomonosov Moscow State University, Lomonosovskiy prospect, 31-5, Moscow 119192, RussiaDepartment of GeneticsFaculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory, 1-12, Moscow 119991, Russia Laboratory of Exercise PhysiologyInstitute of Biomedical Problems, Russian Academy of Sciences, Khoroshevskoye shosse, 76A, Moscow 123007, RussiaFaculty of Fundamental MedicineM.V. Lomonosov Moscow State University, Lomonosovskiy prospect, 31-5, Moscow 119192, RussiaDepartment of GeneticsFaculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory, 1-12, Moscow 119991, Russia danil-popov@yandex.ru.
authors: Daniil V
authors: DV
authors: Popov
authors: Laboratory of Exercise PhysiologyInstitute of Biomedical Problems, Russian Academy of Sciences, Khoroshevskoye shosse, 76A, Moscow 123007, RussiaFaculty of Fundamental MedicineM.V. Lomonosov Moscow State University, Lomonosovskiy prospect, 31-5, Moscow 119192, RussiaDepartment of GeneticsFaculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory, 1-12, Moscow 119991, Russia.
authors: Evgeny A
authors: EA
authors: Lysenko
authors: Laboratory of Exercise PhysiologyInstitute of Biomedical Problems, Russian Academy of Sciences, Khoroshevskoye shosse, 76A, Moscow 123007, RussiaFaculty of Fundamental MedicineM.V. Lomonosov Moscow State University, Lomonosovskiy prospect, 31-5, Moscow 119192, RussiaDepartment of GeneticsFaculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory, 1-12, Moscow 119991, Russia.
authors: Tatiana F
authors: TF
authors: Vepkhvadze
authors: Laboratory of Exercise PhysiologyInstitute of Biomedical Problems, Russian Academy of Sciences, Khoroshevskoye shosse, 76A, Moscow 123007, RussiaFaculty of Fundamental MedicineM.V. Lomonosov Moscow State University, Lomonosovskiy prospect, 31-5, Moscow 119192, RussiaDepartment of GeneticsFaculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory, 1-12, Moscow 119991, Russia.
authors: Nadia S
authors: NS
authors: Kurochkina
authors: Laboratory of Exercise PhysiologyInstitute of Biomedical Problems, Russian Academy of Sciences, Khoroshevskoye shosse, 76A, Moscow 123007, RussiaFaculty of Fundamental MedicineM.V. Lomonosov Moscow State University, Lomonosovskiy prospect, 31-5, Moscow 119192, RussiaDepartment of GeneticsFaculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory, 1-12, Moscow 119991, Russia.
authors: Pavel A
authors: PA
authors: Maknovskii
authors: Laboratory of Exercise PhysiologyInstitute of Biomedical Problems, Russian Academy of Sciences, Khoroshevskoye shosse, 76A, Moscow 123007, RussiaFaculty of Fundamental MedicineM.V. Lomonosov Moscow State University, Lomonosovskiy prospect, 31-5, Moscow 119192, RussiaDepartment of GeneticsFaculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory, 1-12, Moscow 119991, Russia Laboratory of Exercise PhysiologyInstitute of Biomedical Problems, Russian Academy of Sciences, Khoroshevskoye shosse, 76A, Moscow 123007, RussiaFaculty of Fundamental MedicineM.V. Lomonosov Moscow State University, Lomonosovskiy prospect, 31-5, Moscow 119192, RussiaDepartment of GeneticsFaculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory, 1-12, Moscow 119991, Russia.
authors: Olga L
authors: OL
authors: Vinogradova
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D056352:Athletes; D001483:Base Sequence; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004789:Enzyme Activation / Q000235:genetics; D015444:Exercise; D005091:Exons / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D018482:Muscle, Skeletal / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000235:genetics*; D017423:Sequence Analysis, RNA; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D024363:Transcription Initiation Site; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors; D017868:Cyclic AMP-Dependent Protein Kinases; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D048051:p38 Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases
keywords: PGC-1α; alternative promoter; exercise; skeletal muscle