In humans, aberrant upregulation of FRG1 expression, via epigenetic dysregulation of the FSHD-associated chromosome 4q35 region and, as recently discovered, through the binding of DUX4-FL, has long been a proposed disease mechanism for FSHD [36, 41, 88]. Here, DUX4 is linked to facioscapulohumeral muscular dystrophy.