Novel epigenetic regulation of skeletal muscle myosin heavy chain genes. Focus on “Differential epigenetic modifications of histones at the myosin heavy chain genes in fast and slow skeletal muscle fibers and in response to muscle unloading”

skeletal muscle is a highly plastic tissue, capable of responding and adapting to a variety of physiological stimuli, e.g., muscle loading and unloading. Multiple functional phenotypes of skeletal muscle exist throughout the body at the same time. For example, muscles required for antigravity support of the skeleton or sustained locomotion are generally slow-contracting, low force-generating, and relatively resistant to fatigue, while other muscles required for quick, powerful movements are generally fast-contracting, high force-generating, and easily fatigued. In fact, skeletal muscle phenotypes have been characterized using combinations of muscle properties, including metabolic, fatigability, color, innervation, or predominant contractile protein expression. Myosin heavy chain (MHC) is the most abundant protein in skeletal muscle, comprising ∼25% of the total protein content, and is a major component of the complex responsible for generating contractile force in skeletal muscle. At least nine MHC isoforms, each transcribed from their own gene, exist in mammalian striated muscle; but only slow type I MHC and various isoforms of fast type II (IIa, IIx/d, and IIb MHC isoforms) are present in adult limb skeletal muscle that is not undergoing regeneration (16). It is well established that skeletal muscle phenotype, particularly MHC gene expression, can be altered by different states of muscular activity or inactivity, as well as various hormonal and metabolic factors (1).