Acute Exercise Remodels Promoter Methylation in Human Skeletal Muscle

“Evidence has emerged to support a physiological role of non-CpG methylation (Lister et al., 2009; Ramsahoye et al., 2000; Woodcock et al., 1988), notably in stems cells, where drastic remodeling of the epigenome occurs (Bird, 2007).”

“DNAmethylation is thought to be mitotically stable, and hence environmental factors were assumed to be unlikely candidates to induce substantial and sustained changes in DNAmethylation in adult tissues (Reik et al., 2001).”

“, 1988), notably in stems cells, where drastic remodeling of the epigenome occurs (Bird, 2007).”

“Evidence is emerging that epigenetic modifications through DNA methylation contribute to the increased risk and development of metabolic disease by modifying the expression of genes controlling whole body energy and glucose homeostasis (Barrès et al., 2009; Klose and Bird, 2006).”

“DNA methylation is a major epigenetic modification that suppresses gene expression by modulating the access of the transcription machinery to the chromatin or by recruiting methyl binding proteins (Cedar and Bergman, 2009).”

“Digested DNA (4 mg) was used for a standard MeDIP assay as described (Weber et al., 2005) and 1–2 mg for methylcytosine capture.”

“Evidence has emerged to support a physiological role of non-CpG methylation (Lister et al., 2009; Ramsahoye et al., 2000; Woodcock et al., 1988), notably in stems cells, where drastic remodeling of the epigenome occurs (Bird, 2007).”

“DNA methyl transferases 3A and 3B (DNMT3A and DNMT3B, also called de novo methyl transferases) possess demethylase activity, but the biochemical sequence is unknown (Kangaspeska et al., 2008; Métivier et al., 2008).”

“Exercise increases the messenger RNA (mRNA) expression and protein levels of a plethora of genes regulating mitochondrial function and fuel usage, including PGC-1a, transcription factor A, mitochondrial (TFAM); peroxisome proliferator-activated receptor d (PPAR-d); and pyruvate dehydrogenase kinase, isoenzyme 4 (PDK4)…”

“(Coffey and Hawley, 2007).”

“The bisulfite modification technique used in this study does not distinguish between methylated and hydroxyl methylated cytosines (Huang et al., 2010).”

“DNA methyl transferases 3A and 3B (DNMT3A and DNMT3B, also called de novo methyl transferases) possess demethylase activity, but the biochemical sequence is unknown (Kangaspeska et al., 2008; Métivier et al., 2008).”

“Exercise increases the messenger RNA (mRNA) expression and protein levels of a plethora of genes regulating mitochondrial function and fuel usage, including PGC-1a, transcription factor A, mitochondrial (TFAM); peroxisome proliferator-activated receptor d (PPAR-d); and pyruvate dehydrogenase kinase, isoenzyme 4 (PDK4)…”

“Regular physical activity reduces the risk for cardiovascular diseases, type 2 diabetes, multiple cancers, depression, obesity, and musculoskeletal diseases (Thune et al., 1997).”

“Evidence is emerging that epigenetic modifications through DNA methylation contribute to the increased risk and development of metabolic disease by modifying the expression of genes controlling whole body energy and glucose homeostasis (Barrès et al., 2009; Klose and Bird, 2006).”

“Exercise increases the messenger RNA (mRNA) expression and protein levels of a plethora of genes regulating mitochondrial function and fuel usage, including PGC-1a, transcription factor A, mitochondrial (TFAM); peroxisome proliferator-activated receptor d (PPAR-d); and pyruvate dehydrogenase kinase, isoenzyme 4 (PDK4)…”

“Bisulfite treatment was performed as described (Olek et al., 1996), with the following adaptations: 1 mg of genomic DNA was embedded in a 2% Low Melting Point Agarose solution and 10 beads were formed.”

“Exercise increases the messenger RNA (mRNA) expression and protein levels of a plethora of genes regulating mitochondrial function and fuel usage, including PGC-1a, transcription factor A, mitochondrial (TFAM); peroxisome proliferator-activated receptor d (PPAR-d); and pyruvate dehydrogenase kinase, isoenzyme 4 (PDK4)…”

“Luminometric Methylation Assay For LUMA interrogation of CpG methylation within the CCGG sequence, experimental conditions are described (Karimi et al., 2006).”

“By increasing the elevation of cytoplasmic Ca2+ levels, caffeine mimics exercise-induced expression of genes related to mitochondrial function in L6 myotubes (Ojuka et al., 2003).”

“The CXXC domain-containing enzyme TET1 has been described to participate in DNA demethylation through modifying 50-hydroxylase activity (Zhang et al., 2010).”

“Soleus muscles were removed from anesthetized and fed female C57BL/6 mice and incubated at 30 C for 10 min as previously described (Treebak et al., 2007) in oxygenated (95% O2 and 5% CO2) Krebs-Henseleit bicarbonate buffer (containing 8 mM mannitol, 5 mM glucose, and 0.1% BSA) in a Myograph system…”

“Exercise increases the messenger RNA (mRNA) expression and protein levels of a plethora of genes regulating mitochondrial function and fuel usage, including PGC-1a, transcription factor A, mitochondrial (TFAM); peroxisome proliferator-activated receptor d (PPAR-d); and pyruvate dehydrogenase kinase, isoenzyme 4 (PDK4)…”

“Dantrolene blocks caffeine-induced gene expression by inhibiting Ca2+ release from the sarcoplasmic reticulum (Ojuka et al., 2002; Van Winkle, 1976).”

“Consistent with previous results (Kusuhara et al., 2007; Ojuka et al., 2002), ionomycin increased mRNA”

“Evidence has emerged to support a physiological role of non-CpG methylation (Lister et al., 2009; Ramsahoye et al., 2000; Woodcock et al., 1988), notably in stems cells, where drastic remodeling of the epigenome occurs (Bird, 2007).”

“For example, the naturally occurring short-chain fatty acid butyrate acutely alters histone deacetylase activity and DNA methylation status in normal (Parker et al., 1986) and cancercell lines (de Haan et al., 1986; Stoddart et al., 1989).”

“Another level of regulation of mRNA and protein abundance by exercise involves alterations in DNA methylation status (Barrès et al., 2012), histone modifications (McGee and Hargreaves, 2011), and microRNA expression (Zacharewicz et al.”

“Recent studies showing that acute exercise, overfeeding, and type 2 diabetes can modulate gene expression in skeletal muscle through epigenetic mechanisms [71-73] open the exciting scenario that lifestyle factors can interact with developmental programming to regulate adipose tissue mass and distribution.”