Facioscapulohumeral muscular dystrophy and DUX4: breaking the silence.

Publication Type:

Journal Article


Trends in molecular medicine, Volume 17, Issue 5, p.252-8 (2011)


2011, chromatin, Epigenomics, Gene Silencing, Homeodomain Proteins, Human Biology Division, Humans, Microsatellite Repeats, Models, Genetic, Muscular Dystrophy, Facioscapulohumeral, Transcription, Genetic


Autosomal dominant facioscapulohumeral muscular dystrophy (FSHD) has an unusual pathogenic mechanism. FSHD is caused by deletion of a subset of D4Z4 macrosatellite repeat units in the subtelomere of chromosome 4q. Recent studies provide compelling evidence that a retrotransposed gene in the D4Z4 repeat, DUX4, is expressed in the human germline and then epigenetically silenced in somatic tissues. In FSHD, the combination of inefficient chromatin silencing of the D4Z4 repeat and polymorphisms on the FSHD-permissive alleles that stabilize the DUX4 mRNAs emanating from the repeat result in inappropriate DUX4 protein expression in muscle cells. FSHD is thereby the first example of a human disease caused by the inefficient repression of a retrogene in a macrosatellite repeat array.