title: Increasing D4Z4 repeat copy number compromises C2C12 myoblast differentiation.
abstract: Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant myopathy associated with deletions of a subtelomeric repeat (D4Z4). A reduction in D4Z4 copy number coincides with increased expression of neighboring 4q35 genes, implying a normal repressive role for the repeats. Here we examine the effect of increasing D4Z4 repeat number on reporter gene activity in C2C12 cells. Repeat size had only a minor cis-effect on reporter gene activity but greatly compromised myotube formation. This latter trans-effect did not result from expression of a gene within the repeat (DUX4) but likely results from squelching of the D4Z4 recognition complex.
authors.affiliation: Molecular Medicine Program, Ottawa Health Research Institute, 501 Smyth Road, Ottawa, ON, Canada K1H 8L6.
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Yip
authors.forename: David J
authors.initials: DJ
authors.lastname: Picketts
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D003001:Cloning, Molecular; D003360:Cosmids; D017930:Genes, Reporter; D006801:Humans; D008561:Membrane Fusion; D020391:Muscular Dystrophy, Facioscapulohumeral / Q000235:genetics; D032446:Myoblasts / Q000166:cytology*; D012091:Repetitive Sequences, Nucleic Acid; D017384:Sequence Deletion; D016615:Telomere / Q000235:genetics*