The genetic lesions that cause FSHD disrupt these regulatory pathways resulting in D4Z4 DNA hypomethylation; reduced H3K9me2/3 and H3K27me3 levels; and loss of HP1γ, EZH2, SMCHD1 and cohesin binding; which together culminate in ectopic DUX4 expression (Cabianca et al., 2012; Daxinger et al., 2015; Jones et al., 2014; Lemmers et al., 2012; van den Boogaard et al., 2016; van Overveld et al., 2003; Zeng et al., 2009). Here, DUX4 is linked to facioscapulohumeral muscular dystrophy.