Notably, depletion of NuRD and CAF-1 complex components did not lead to DUX4 de-repression in the parental HFF3 fibroblast line, whereas the HFF3 iPS lines responded similarly to the eMHF2 iPS line (Figure 5—figure supplement 3). These results indicate that the NuRD and CAF-1 complexes that silence the D4Z4 macrosatellite array in muscle cells also contribute to the regulation of this locus in human iPS cells, and that iPS cells have decreased D4Z4 repression compared to their somatic counterpart, similar to the decreased repression in FSHD myoblasts compared to control myoblasts. This evidence concerns the gene CHAF1B and facioscapulohumeral muscular dystrophy.