Therefore, augmented DUX4 expression followingUPF1 KD in myotubes could be due to increases in DUX4 mRNA in nucleithat are already DUX4+ and/or increases in the fraction of DUX4+ nuclei.Immunostaining of FSHD myotubes revealed that the fraction of DUX4+ nucleiincreased from 0.3% to 2.1% following UPF1 KD, a substantialorder-of-magnitude increase (Figure 3G).Together, our data show that NMD is an endogenous suppressor of DUX4 mRNA levels thatcontributes to the very low and variegated expression of DUX4, acharacteristic feature of FSHD muscle cells. The gene discussed is UPF1; the disease is facioscapulohumeral muscular dystrophy.