title: Dynamic changes in global and gene-specific DNA methylation during hibernation in adult thirteen-lined ground squirrels, Ictidomys tridecemlineatus.
abstract: Hibernating mammals conserve energy in the winter by undergoing prolonged bouts of torpor, interspersed with brief arousals back to euthermia. These bouts are accompanied by a suite of reversible physiological and biochemical changes; however, much remains to be discovered about the molecular mechanisms involved. Given the seasonal nature of hibernation, it stands to reason that underlying plastic epigenetic mechanisms should exist. One such form of epigenomic regulation involves the reversible modification of cytosine bases in DNA by methylation. DNA methylation is well known to be a mechanism that confers upon DNA its cellular identity during differentiation in response to innate developmental cues. However, it has recently been hypothesized that DNA methylation also acts as a mechanism for adapting genome function to changing external environmental and experiential signals over different time scales, including during adulthood. Here, we tested the hypothesis that DNA methylation is altered during hibernation in adult wild animals. This study evaluated global changes in DNA methylation in response to hibernation in the liver and skeletal muscle of thirteen-lined ground squirrels along with changes in expression of DNA methyltransferases (DNMT1/3B) and methyl binding domain proteins (MBDs). A reduction in global DNA methylation occurred in muscle during torpor phases whereas significant changes in DNMTs and MBDs were seen in both tissues. We also report dynamic changes in DNA methylation in the promoter of the myocyte enhancer factor 2C (mef2c) gene, a candidate regulator of metabolism in skeletal muscle. Taken together, these data show that genomic DNA methylation is dynamic across torpor-arousal bouts during winter hibernation, consistent with a role for this regulatory mechanism in contributing to the hibernation phenotype.
authors.affiliation: Department of Pharmacology, McGill University, 3655 Sir William Osler Suite 1309, Montreal, QC, Canada H3G 1Y6; Sackler program in Epigenetics and Psychobiology at McGill University.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Alvarado
authors.affiliation: Department of Pharmacology, McGill University, 3655 Sir William Osler Suite 1309, Montreal, QC, Canada H3G 1Y6; Sackler program in Epigenetics and Psychobiology at McGill University.
authors.forename: Timothy
authors.initials: T
authors.lastname: Mak
authors.affiliation: Department of Pharmacology, McGill University, 3655 Sir William Osler Suite 1309, Montreal, QC, Canada H3G 1Y6; Sackler program in Epigenetics and Psychobiology at McGill University.
authors.forename: Sara
authors.initials: S
authors.lastname: Liu
authors.affiliation: Institute of Biochemistry and Department of Biology, Carleton University, 1125 Colonel By Drive, Ottawa, ON, Canada K1S 5B6.
authors.forename: Kenneth B
authors.initials: KB
authors.lastname: Storey
authors.affiliation: Department of Pharmacology, McGill University, 3655 Sir William Osler Suite 1309, Montreal, QC, Canada H3G 1Y6; Sackler program in Epigenetics and Psychobiology at McGill University moshe.szyf@mcgill.ca.
authors.forename: Moshe
authors.initials: M
authors.lastname: Szyf
mesh_terms: D000818:Animals; D004247:DNA / Q000235:genetics; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D006605:Hibernation / Q000502:physiology*; D008099:Liver / Q000502:physiology; D008297:Male; D018482:Muscle, Skeletal / Q000502:physiology; D018006:Myogenic Regulatory Factors / Q000235:genetics / Q000378:metabolism; D012589:Sciuridae / Q000235:genetics / Q000502:physiology*; D012621:Seasons
chemical_list: D004268:DNA-Binding Proteins; D018006:Myogenic Regulatory Factors; D004247:DNA
keywords: Arousal; Cytosine; Epigenetics; Torpor