Previously, it has been shown by different approaches, including the application of antisense oligonucleotides, DNA nucleases and U7 small nuclear RNA (snRNA), that interference with the usage of the endogenous 4qA DUX4 PAS in myogenic cells derived from FSHD patients results in transcriptional downregulation of DUX4 and its target genes,29, 30, 31, 32, 33 further emphasizing the necessity of the annotated 4qA DUX4 PAS for proper 3′ end processing of DUX4 pre-mRNA and suggesting that interfering with its usage is sufficient to alleviate the FSHD expression signature in myogenic cells. This evidence concerns the gene DUX4 and facioscapulohumeral muscular dystrophy.