Therefore, we tested its role in D4Z4 repeat repression and found that SIN3A or SIN3B depletion led to the activation of DUX4 and DUX4 target genes in FSHD cells (Figure 4—figure supplement 4B–G), supporting a role for the SIN3 complex in D4Z4 regulation. Here, SIN3B is linked to facioscapulohumeral muscular dystrophy.