Whilst Myf5 mRNA was shown to be upregulated by DUX4 possibly representing a compensatory mechanism, Knopp et al. (2016), who analyzed transgenic mice carrying a human D4Z4 genomic locus from an FSHD-affected individual, showed that DUX4 inhibits both MyoD and MyoG gene expression to produce a differentiation defect that cannot be controlled by upregulation of Myf5. DUX4 and its transcriptional activity can be discovered in differentiating human myoblasts [32, 78, 143–145]. Here, DUX4 is linked to facioscapulohumeral muscular dystrophy.