@article{159dd30e9b2042a7ba0a6cf7fddccf2c,
title = "Telomere position effect regulates DUX4 in human facioscapulohumeral muscular dystrophy",
abstract = "Telomeres may regulate human disease by at least two independent mechanisms. First, replicative senescence occurs once short telomeres generate DNA-damage signals that produce a barrier to tumor progression. Second, telomere position effects (TPE) could change gene expression at intermediate telomere lengths in cultured human cells. Here we report that telomere length may contribute to the pathogenesis of facioscapulohumeral muscular dystrophy (FSHD). FSHD is a late-onset disease genetically residing only 25-60 kilobases from the end of chromosome 4q. We used a floxable telomerase to generate isogenic clones with different telomere lengths from affected patients and their unaffected siblings. DUX4, the primary candidate for FSHD pathogenesis, is upregulated over ten-fold in FSHD myoblasts and myotubes with short telomeres, and its expression is inversely proportional to telomere length. FSHD may be the first known human disease in which TPE contributes to age-related phenotype.",
author = "Guido Stadler and Fedik Rahimov and King, {Oliver D.} and Chen, {Jennifer C J} and Robin, {Jerome D.} and Wagner, {Kathryn R.} and Shay, {Jerry W.} and Emerson, {Charles P.} and Wright, {Woodring E.}",
note = "Funding Information: All authors were supported by the Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center (US National Institutes of Health 5U54HD060848). Additional support was provided by the Austrian Science Fund and the American Federation for Aging Research (G.S.), AG01228 from the US National Institute of Aging (W.E.W.), the Muscular Dystrophy Association (F.R.) and P50 CA70907 from the US National Institutes of Health (J.W.S.). We thank D. Leung (Center for Genetic Muscle Disorders, Kennedy Krieger Institute, Johns Hopkins School of Medicine, Baltimore, Maryland, USA) for obtaining phenotypes and muscle biopsies along with K.R.W., G. Bibat (Kennedy Krieger Institute, Johns Hopkins School of Medicine Baltimore, Maryland, USA) and D. Perez (FSH Society, Lexington, Massachusetts, USA) for subject recruitment and outreach, N. Liu for technical assistance, T. Jones for discussions and S. van der Maarel (Leiden University Medical Center, Leiden, Netherlands) and A. Belayew (University of Mons, Mons, Belgium) for reporter constructs.",
year = "2013",
month = jun,
doi = "10.1038/nsmb.2571",
language = "English (US)",
volume = "20",
pages = "671--678",
journal = "Nature Structural and Molecular Biology",
issn = "1545-9993",
publisher = "Nature Publishing Group",
number = "6",
}