Epigenetics of muscle disorders

As heritable information apart from the DNA sequence itself, epigenetics represents a higher level of complexity in the regulation of gene expression and allows for a wide range of outputs. Epigenetics is a very powerful tool by which cells quickly fine tune the expressions of genes in response to environmental changes or permanently turn off other genes by inactivating their expression or inhibiting their translation. Muscle tissue varies with its function and location in the body. In mammals there are three types of muscle tissues: cardiac, skeletal, and smooth muscle. The first two are striated and display an orderly arrangement of myofibrils in sarcomeres. In contrast, in smooth muscle, the myofilaments are not aligned into sarcomeres. Smooth and cardiac muscles contract involuntarily under the control of the autonomic nervous system and endocrine and hormonal signals. In contrast, skeletal muscle only contracts voluntarily under the influence of the central nervous system. Several epigenetic mechanisms have been shown to regulate both the development and the responses to external stimuli of all muscle tissues. Regarding histone modifications alone, we should mention the existence of numerous epigenetic markers, such as histone methylation, ubiquitylation, phosphorylation, sumoylation, ribosylation, citrullination and acetylation, which affect chromatin structure and, consequently, gene expression. By limiting the discussion to the epigenetic mechanisms of DNA methylation, histone acetylation and methylation, and noncoding RNAs, we review how these processes regulate aspects of adult muscle remodeling. Indeed, all three types of muscles are subjected to changes in shape, mass, and metabolism in adulthood in response to external input. Epigenetics has been demonstrated to mediate many of these adaptations. In this chapter, we will summarize how epigenetics influences cardiac, skeletal, and smooth muscle cell physiologies, and we will review the epigenetic mechanisms that are altered in motor neuron diseases, muscular dystrophies, and rhabdomyosarcoma (RMS) and highlight the potential usefulness of epigenetic drugs for the treatment of muscle disorders.