Novel Mechanisms Regulating Myogenic Differentiation in Skeletal Muscle

Abstract

Skeletal muscle has a characteristic differentiation process involving cell fusion. The molecular mechanisms that regulate this differentiation remain to be elucidated. Muscle differentiation starting from satellite cells is hierarchically regulated by a network of myogenic transcription factors（TFs）depending on the stage of differentiation. The function of these TFs has been found to be highly dependent on chromatin structure（i.e., chromatin remodeling），which is altered various epigenetic regulatory mechanisms. Furthermore, novel mechanisms that regulate the chromatin remodeling, such as pioneer TFs, DNA strand breaks, and non-coding RNAs, are being elucidated to operate at each stage of muscle differentiation. The accumulation of such basic knowledge has contributed greatly to an integrated understanding of the regulatory mechanisms of differentiation in skeletal muscle. The pathological deterioration of skeletal muscles, represented by sarcopenia, is a risk factor for death and need for nursing care in the elderly, but currently only symptomatic treatment is available. The establishment of a molecular basis underlying the muscle differentiation will accelerate the development of fundamental therapeutic and preventive measures based on such molecular pathogenesis.