DUX4, a homeobox-containing gene present in a tandem array, is implicated in 
facioscapulohumeral muscular dystrophy (FSHD), a dominant autosomal disease. New 
findings about DUX4 have raised as many fundamental questions about the 
molecular pathology of this unique disease as they have answered. This review 
discusses recent studies addressing the question of whether there is extensive 
FSHD-related transcription dysregulation in adult-derived myoblasts and 
myotubes, the precursors for muscle repair. Two models for the role of DUX4 in 
FSHD are presented. One involves transient pathogenic expression of DUX4 in many 
cells in the muscle lineage before the myoblast stage resulting in a persistent, 
disease-related transcription profile ('Majority Rules'), which might be 
enhanced by subsequent oscillatory expression of DUX4. The other model 
emphasizes the toxic effects of inappropriate expression of DUX4 in only an 
extremely small percentage of FSHD myoblasts or myotube nuclei ('Minority 
Rules'). The currently favored Minority Rules model is not supported by recent 
studies of transcription dysregulation in FSHD myoblasts and myotubes. It also 
presents other difficulties, for example, explaining the expression of 
full-length DUX4 transcripts in FSHD fibroblasts. The Majority Rules model is 
the simpler explanation of findings about FSHD-associated gene expression and 
the DUX4-encoded homeodomain-type protein.