New insights into the epigenetic control of satellite cells

Abstract

Epigenetics finely tunes gene expression at a functional level without modifying the DNA sequence, thereby contributing to the complexity of genomic regulation. Satellite cells (SCs) are adult muscle stem cells that are important for skeletal post-natal muscle growth, homeostasis and repair. The understanding of the epigenome of SCs at different stages and of the multiple layers of the post-transcriptional regulation of gene expression is constantly expanding. Dynamic interactions between different epigenetic mechanisms regulate the appropriate timing of muscle-specific gene expression and influence the lineage fate of SCs. In this review, we report and discuss the recent literature about the epigenetic control of SCs during the myogenic process from activation to proliferation and from their commitment to a muscle cell fate to their differentiation and fusion to myotubes. We describe how the coordinated activities of the histone methyltransferase families Polycomb group (PcG), which represses the expression of developmentally regulated genes, and Trithorax group, which antagonizes the repressive activity of the PcG, regulate myogenesis by restricting gene expression in a time-dependent manner during each step of the process. We discuss how histone acetylation and deacetylation occurs in specific loci throughout SC differentiation to enable the time-dependent transcription of specific genes. Moreover, we describe the multiple roles of microRNA, an additional epigenetic mechanism, in regulating gene expression in SCs, by repressing or enhancing gene transcription or translation during each step of myogenesis. The importance of these epigenetic pathways in modulating SC activation and differentiation renders them as promising targets for disease interventions. Understanding the most recent findings regarding the epigenetic mechanisms that regulate SC behavior is useful from the perspective of pharmacological manipulation for improving muscle regeneration and for promoting muscle homeostasis under pathological conditions.

Differences in micro-RNA expression profile between vastus lateralis samples and myotubes in COPD cachexia

“…Among several epigenetic mechanisms, the role of microRNAs in muscle development and myogenesis has been most widely studied in the last decade. MicroRNAs are small, regulatory, non-coding RNA molecules that are mostly located within the cells, although they may also be identified in biological fluids and cell culture media (25). MicroRNAs regulate gene transcription by either inducing RNA silencing or by inhibiting the translation of the target mRNA within the cells.…”

Muscle satellite cells are functionally impaired in myasthenia gravis: consequences on muscle regeneration

“…Since these effects were still observed in vitro, in the absence of paracrine factors, it is likely that intrinsic mechanisms could explain the observed high proliferation and differentiation of SCs. Moresi et al [49,50] have reported epigenetic changes in SCs during the myogenic processes from activation to proliferation and from proliferation to differentiation. They described the activities of the histone methylation, acetylation, and deacetylation that modulate the transcription of specific genes or the role of microRNA enhancing or repressing transcription factors during myogenesis.…”

HDAC4 Regulates the Proliferation, Differentiation and Apoptosis of Chicken Skeletal Muscle Satellite Cells

“…For birds, the number of muscle fibers is determined at birth and postnatal muscle growth is due to hypertrophy or an increase in muscle fiber size, which is accompanied by the proliferative activity of the skeletal muscle satellite cell (SMSC). SMSCs are the kind of pluripotent stem cells that with the ability to proliferate and differentiate could be transformed from a quiescent state into mature muscle fibers under appropriate stimulation [2,3]. Thus, the repair and regeneration of skeletal muscles after injury mainly depends on SMSCs [2,4].…”

“…SMSCs are the kind of pluripotent stem cells that with the ability to proliferate and differentiate could be transformed from a quiescent state into mature muscle fibers under appropriate stimulation [2,3]. Thus, the repair and regeneration of skeletal muscles after injury mainly depends on SMSCs [2,4]. It is well-known that growth of SMSCs is regulated by a complex set of biological processes, including many genes [5,6].…”