title: Differences in histone modifications between slow- and fast-twitch muscle of adult rats and following overload, denervation, or valproic acid administration.
abstract: Numerous studies have reported alterations in skeletal muscle properties and phenotypes in response to various stimuli such as exercise, unloading, and gene mutation. However, a shift in muscle fiber phenotype from fast twitch to slow twitch is not completely induced by stimuli. This limitation is hypothesized to result from the epigenetic differences between muscle types. The main purpose of the present study was to identify the differences in histone modification for the plantaris (fast) and soleus (slow) muscles of adult rats. Genome-wide analysis by chromatin immunoprecipitation followed by DNA sequencing revealed that trimethylation at lysine 4 and acetylation of histone 3, which occurs at transcriptionally active gene loci, was less prevalent in the genes specific to the slow-twitch soleus muscle. Conversely, gene loci specific to the fast-twitch plantaris muscle were associated with the aforementioned histone modifications. We also found that upregulation of slow genes in the plantaris muscle, which are related to enhanced muscular activity, is not associated with activating histone modifications. Furthermore, silencing of muscle activity by denervation caused the displacement of acetylated histone and RNA polymerase II (Pol II) in 5' ends of genes in plantaris, but minor effects were observed in soleus. Increased recruitment of Pol II induced by forced acetylation of histone was also suppressed in valproic acid-treated soleus. Our present data indicate that the slow-twitch soleus muscle has a unique set of histone modifications, which may relate to the preservation of the genetic backbone against physiological stimuli.
authors.affiliation: Graduate School of Health Sciences, Matsumoto University, Matsumoto, Nagano, Japan; fuminori.kawano@matsu.ac.jp.
authors.forename: Fuminori
authors.initials: F
authors.lastname: Kawano
authors.affiliation: Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan;
authors.forename: Keisuke
authors.initials: K
authors.lastname: Nimura
authors.affiliation: Center for Medical Research and Education, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan;
authors.forename: Saki
authors.initials: S
authors.lastname: Ishino
authors.affiliation: School of Human Cultures, University of Shiga Prefecture, Hikone, Shiga, Japan;
authors.forename: Naoya
authors.initials: N
authors.lastname: Nakai
authors.affiliation: Medicine for Sports and Performing Arts, Graduate School of Medicine, Osaka University, Toyonaka, Osaka, Japan; and.
authors.forename: Ken
authors.initials: K
authors.lastname: Nakata
authors.affiliation: Graduate School of Sports Sciences, Doshisha University, Kyotanabe City, Kyoto, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Ohira
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D003714:Denervation / Q000379:methods; D019417:Hindlimb Suspension / Q000379:methods / Q000502:physiology; D042421:Histone Code / Q000502:physiology*; D008297:Male; D018656:Muscle Fibers, Fast-Twitch / Q000187:drug effects / Q000502:physiology*; D018657:Muscle Fibers, Slow-Twitch / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000294:innervation* / Q000502:physiology*; D009133:Muscular Atrophy / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014635:Valproic Acid / Q000633:toxicity*
chemical_list: D014635:Valproic Acid
keywords: epigenetics; fast and slow skeletal muscle; gene expression; muscle activity