View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Developmental Cell Article DUX4 Activates Germline Genes, Retroelements, and Immune Mediators: Implications for Facioscapulohumeral Dystrophy Linda N. Geng,1,7 Zizhen Yao,2,7 Lauren Snider,1 Abraham P. Fong,1 Jennifer N. Cech,1 Janet M. Young,1 Silvere M. van der Maarel,3 Walter L. Ruzzo,4 Robert C. Gentleman,5 Rabi Tawil,6 and Stephen J. Tapscott1,* 1Division of Human Biology 2Division of Public Health Sciences Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA 3Department of Human Genetics, Leiden University Medical Center, 2333ZA Leiden, The Netherlands 4Departments of Computer Science and Engineering and Genome Sciences, University of Washington, Seattle, WA 98105, USA 5Bioinformatics and Computational Biology, Genentech, South San Francisco, CA 94080, USA 6Department of Neurology, University of Rochester, Rochester, NY 14627, USA 7These authors contributed equally to this work *Correspondence:
[email protected] DOI 10.1016/j.devcel.2011.11.013 SUMMARY 1996). Each repeat unit contains a copy of the double homeobox retrogene DUX4 (Clapp et al., 2007; Gabrie¨ ls et al., 1999; Lyle Facioscapulohumeral dystrophy (FSHD) is one of et al., 1995), and inappropriate expression of DUX4 was initially the most common inherited muscular dystrophies. proposed as a possible cause of FSHD. This was supported The causative gene remains controversial and the by the observations that repeat contraction is associated with mechanism of pathophysiology unknown. Here we decreased repressive epigenetic marks in the remaining D4Z4 identify genes associated with germline and early units (van Overveld et al., 2003; Zeng et al., 2009) and that over- stem cell development as targets of the DUX4 tran- expression of the DUX4 protein in a variety of cells, including skeletal muscle, causes apoptotic cell death (Kowaljow et al., scription factor, a leading candidate gene for FSHD.