Muscle injury causes long-term changes in stem-cell DNA methylation

Abstract

Injury to muscle brings about the activation of stem cells, which then generate new myocytes to replace damaged tissue. We demonstrate that this activation is accompanied by a dramatic change in the stem-cell methylation pattern that prepares them epigenetically for terminal myocyte differentiation. These de- and de novo methylation events occur at regulatory elements associated with genes involved in myogenesis and are necessary for activation and regeneration. Local injury of one muscle elicits an almost identical epigenetic change in satellite cells from other muscles in the body, in a process mediated by circulating factors. Furthermore, this same methylation state is also generated in muscle stem cells (MuSCs) of female animals following pregnancy, even in the absence of any injury. Unlike the activation-induced expression changes, which are transient, the induced methylation profile is stably maintained in resident MuSCs and thus represents a molecular memory of previous physiological events that is probably programmed to provide a mechanism for long-term adaptation.

Epigenetics of Genes Preferentially Expressed in Dissimilar Cell Populations: Myoblasts and Cerebellum

“…Hypertrophy depends on both transcriptional changes in myofiber nuclei and activation of satellite cells [3,5]. Muscle injury can affect DNA methylation profiles of satellite cells [6]. During activation of satellite cells, there are further changes in DNA methylation and in chromatin [6,7].…”

“…Muscle injury can affect DNA methylation profiles of satellite cells [6]. During activation of satellite cells, there are further changes in DNA methylation and in chromatin [6,7]. There is overrepresentation of age-related SkM DMRs in SkM enhancer chromatin and regions around transcription start sites (TSS).…”

“…Epigenetics is also implicated in satellite cell, myoblast, and muscle fiber heterogeneity [8][9][10] and in memory effects for strenuous muscle use and, possibly, for muscle disuse [5,6,11,12]. There are differences in expression profiles and epigenetics for SkM muscle fiber subtypes (e.g., fast or slow), which can interconvert [10].…”