The necessity of the NuRD complex to maintain repression of DUX4 in FSHD cells suggests that the DUX4-mediated induction of the MBD3L family of factors might amplify DUX4 expression within a nucleus or facilitate the internuclear spreading of DUX4 in multinucleated myotubes. Here, DUX4 is linked to facioscapulohumeral muscular dystrophy.