section_path: Exercise-trained effects are mediated by epigenetic mechanisms/Exercise-induced long-term alteration of gene expression by histone acetylation or deacetylation
section_name: Exercise-induced long-term alteration of gene expression by histone acetylation or deacetylation
paragraph_text: Exercise-induced long-term alteration of gene expression by histone acetylation or deacetylation
  
  As indicated above, after exercise, epigenetic alterations to enhancers alter long-term expression of hundreds of muscle genes. This includes genes producing proteins secreted into the systemic circulation, many of which may act as endocrine messengers. Six sedentary, about 23 years old, Caucasian males provided vastus lateralis (a thigh muscle) biopsies before entering an exercise program (six weeks of 60-minute sessions of riding a stationary cycle, five days per week). Four days after this exercise program was completed, the expression of many genes was persistently epigentically altered. The alterations altered acetylations and deacetylations of the histone tails located in the enhancers controlling the genes with altered expression.
  
  Up-regulated genes were associated with epigenetic acetylations added at histone 3 lysine 27 (H3K27ac) of nucleosomes located at their enhancers. Down-regulated genes were associated with the removal of epigenetic acetylations at H3K27 in nucleosomes located at their enhancers (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 the exercise training program. Four days after the exercise program was completed, biopsies of the same muscles showed 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 (multiple enhancers were found connected to some genes), where both the enhancer and the connected target gene were coordinately either upregulated or downregulated after exercise training.