{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Geng LN"],"funding":["NICHD NIH HHS","NCRR NIH HHS","NINDS NIH HHS","NIAMS NIH HHS"],"pagination":["38-51"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3264808"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["22(1)"],"pubmed_abstract":["Facioscapulohumeral dystrophy (FSHD) is one of the most common inherited muscular dystrophies. The causative gene remains controversial and the mechanism of pathophysiology unknown. Here we identify genes associated with germline and early stem cell development as targets of the DUX4 transcription factor, a leading candidate gene for FSHD. The genes regulated by DUX4 are reliably detected in FSHD muscle but not in controls, providing direct support for the model that misexpression of DUX4 is a causal factor for FSHD. Additionally, we show that DUX4 binds and activates LTR elements from a class of MaLR endogenous primate retrotransposons and suppresses the innate immune response to viral infection, at least in part through the activation of DEFB103, a human defensin that can inhibit muscle differentiation. These findings suggest specific mechanisms of FSHD pathology and identify candidate biomarkers for disease diagnosis and progression."],"journal":["Developmental cell"],"pubmed_title":["DUX4 activates germline genes, retroelements, and immune mediators: implications for facioscapulohumeral dystrophy."],"pmcid":["PMC3264808"],"funding_grant_id":["K12 HD043376-08","UL1 RR024160","R01AR045203","K12 HD043376","P01 NS069539","UL1 RR024160-02","R01 AR045203-13","P01 NS069539-03","R01 AR045203","P01NS069539","U5K12HD043376-08"],"pubmed_authors":["Cech JN","Tawil R","Yao Z","Snider L","Fong AP","Geng LN","Gentleman RC","Young JM","van der Maarel SM","Ruzzo WL","Tapscott SJ"],"additional_accession":[]},"is_claimable":false,"name":"DUX4 activates germline genes, retroelements, and immune mediators: implications for facioscapulohumeral dystrophy.","description":"Facioscapulohumeral dystrophy (FSHD) is one of the most common inherited muscular dystrophies. The causative gene remains controversial and the mechanism of pathophysiology unknown. Here we identify genes associated with germline and early stem cell development as targets of the DUX4 transcription factor, a leading candidate gene for FSHD. The genes regulated by DUX4 are reliably detected in FSHD muscle but not in controls, providing direct support for the model that misexpression of DUX4 is a causal factor for FSHD. Additionally, we show that DUX4 binds and activates LTR elements from a class of MaLR endogenous primate retrotransposons and suppresses the innate immune response to viral infection, at least in part through the activation of DEFB103, a human defensin that can inhibit muscle differentiation. These findings suggest specific mechanisms of FSHD pathology and identify candidate biomarkers for disease diagnosis and progression.","dates":{"release":"2012-01-01T00:00:00Z","publication":"2012 Jan","modification":"2024-11-14T10:38:59.314Z","creation":"2019-03-27T00:48:21Z"},"accession":"S-EPMC3264808","cross_references":{"pubmed":["22209328"],"doi":["10.1016/j.devcel.2011.11.013"]}}