We showed that knocking down RUVBL1 in FSHD muscle cells further derepresses DUX4 and provided evidence that some of these proteins may act with SMCHD1 at different genomic sites in a spatiotemporal context, suggesting that SMCHD1 may participate in different chromatin complexes. Here, SMCHD1 is linked to Facioscapulohumeral dystrophy.