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Regulation of PPARGC1A gene expression in trained and untrained human skeletal muscle.
- Source :
-
Physiological reports [Physiol Rep] 2017 Dec; Vol. 5 (23). - Publication Year :
- 2017
-
Abstract
- Promoter-specific expression of the PPARGC1A gene in untrained and trained human skeletal muscle was investigated. Ten untrained males performed a one-legged knee extension exercise (for 60 min) with the same relative intensity both before and after 8 weeks of cycling training. Samples from the m. vastus lateralis of each leg were taken before and after exercise. Postexercise PPARGC1A gene expression via the canonical promoter increased by ~100% ( P  < 0.05) in exercised and nonexercised untrained muscles, but did not change in either leg after training program. In untrained and trained exercised muscle, PPARGC1A gene expression via the alternative promoter increased by two orders of magnitude ( P  < 0.01). We found increases in postexercise content of dephosphorylated (activated) CRTC2, a coactivator of CREB1, in untrained exercised muscle and in expression of CREB1-related genes in untrained and trained exercised muscle ( P  < 0.01-0.05); this may partially explain the increased expression of PPARGC1A via the alternative promoter. In addition, comparison of the regulatory regions of both promoters revealed unique conserved motifs in the alternative promoter that were associated with transcriptional repressors SNAI1 and HIC1. In conclusion, in untrained muscle, exercise-induced expression of the PPARGC1A gene via the canonical promoter may be regulated by systemic factors, while in trained muscle the canonical promoter shows constitutive expression at rest and after exercise. Exercise-induced expression of PPARGC1A via the alternative promoter relates to intramuscular factors and associates with activation of CRTC2-CREB1. Apparently, expression via the alternative promoter is regulated by other transcription factors, particularly repressors.<br /> (© 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)
- Subjects :
- Adult
Conserved Sequence
Humans
Kruppel-Like Transcription Factors metabolism
Male
Muscle, Skeletal physiology
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha genetics
Snail Family Transcription Factors metabolism
Transcription Factors metabolism
Transcriptional Activation
Exercise
Muscle, Skeletal metabolism
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha metabolism
Promoter Regions, Genetic
Subjects
Details
- Language :
- English
- ISSN :
- 2051-817X
- Volume :
- 5
- Issue :
- 23
- Database :
- MEDLINE
- Journal :
- Physiological reports
- Publication Type :
- Academic Journal
- Accession number :
- 29233908
- Full Text :
- https://doi.org/10.14814/phy2.13543