Concise Review: Epigenetic Regulation of Myogenesis in Health and Disease

Abstract

© AlphaMed Press 2016.Skeletal muscle regeneration is initiated by satellite cells, a population of adult stem cells that reside in the muscle tissue. The ability of satellite cells to self-renew and to differentiate into the muscle lineage is under transcriptional and epigenetic control. Satellite cells are characterized by an open and permissive chromatin state. The transcription factor Pax7 is necessary for satellite cell function. Pax7 is a nodal factor regulating the expression of genes associated with satellite cell growth and proliferation, while preventing differentiation. Pax7 recruits chromatin modifiers to DNA to induce expression of specific target genes involved in myogenic commitment following asymmetric division of muscle stem cells. Emerging evidence suggests that replacement of canonical histones with histone variants is an important regulatory mechanism controlling the ability of satellite cells and myoblasts to differentiate. Differentiation into the muscle lineage is associated with a global gene repression characterized by a decrease in histone acetylationwith an increase in repressive histonemarks.However, genes important fordifferentiation areupregulatedbythe specific actionof histone acetyltransferases andother chromatin modifiers, in combination with several transcription factors, including MyoD and Mef2. Treatment with histone deacetylase (HDAC) inhibitors enhances muscle regeneration and is considered as a therapeutic approach in the treatment of muscular dystrophy. This reviewdescribes the recent findings on epigenetic regulation in satellite stemcellsandcommittedmyoblasts.Thepotential of epigenetic drugs,such asHDAC inhibitors, aswell as their molecularmechanism of action in muscle cells, will be addressed.