text: After exercise, epigenetic alterations to enhancers alter long-term expression of hundreds of muscle genes. This includes genes producing proteins and other products secreted into the systemic circulation, many of which may act as endocrine messengers. Of 817 genes with altered expression, 157 (according to Uniprot) or 392 (according to Exocarta) of the proteins produced according to those genes were known to be secreted from the muscles. Four days after an endurance type of exercise, many genes have persistently altered epigentically regulated expression. Four pathways altered were in the platelet/coagulation system, the cognitive system, the cardiovascular system, and the renal system. Epigenetic regulation of these genes was indicated by epigenetic alterations in the distant upstream DNA regulatory sequences of the enhancers of these genes.
  Up-regulated genes had epigenetic acetylations added at histone 3 lysine 27 (H3k27ac) of nucleosomes located at the enhancers controlling those up-regulated genes, while down-regulated genes had epigenetic acetylations removed from H3K27 in nucleosomes located at the enhancers that control those genes (see Figure "A nucleosome with histone tails set for transcriptional activation"). Biopsies of the vastus lateralis muscle showed expression of 13,108 genes at baseline before an exercise training program. Six sedentary 23-year-old Caucasian males provided vastus lateralis biopsies before entering an exercise program (six weeks of 60-minute sessions of riding a stationary cycle, five days per week). Four days after the exercise program was completed, biopsies of the same muscles had altered gene expression, with 641 genes up-regulated and 176 genes down-regulated. Williams et al. identified 599 enhancer-gene interactions, covering 491 enhancers and 268 genes, where both the enhancer and the connected target gene were coordinately either upregulated or downregulated after exercise training.