It is known that contraction of these D4Z4 macro-satellite sequences is associated with decreased cytosine methylation and an open chromatin structure, leading to infrequent sporadic expression of the DUX4 gene in the skeletal muscle that results in facioscapulohumeral muscular dystrophy (FSHD) [54–56] (Fig. 5a). This evidence concerns the gene DUX4 and facioscapulohumeral muscular dystrophy.