Regulation of gene expression in trained and untrained human skeletal muscle.

Promoter-specific expression of the 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 of each leg were taken before and after exercise. Postexercise gene expression via the canonical promoter increased by ~100% ( < 0.05) in exercised and nonexercised untrained muscles, but did not change in either leg after training program. In untrained and trained exercised muscle, gene expression via the alternative promoter increased by two orders of magnitude ( < 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 ( < 0.01-0.05); this may partially explain the increased expression of 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 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 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.