{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T22:43:48Z","timestamp":1791585828258,"version":"4.3.4"},"reference-count":186,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,11,26]],"date-time":"2021-11-26T00:00:00Z","timestamp":1637884800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["RF-2018-12366631"],"award-info":[{"award-number":["RF-2018-12366631"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Joint Programme on Rare Diseases","award":["EJPRD20-191"],"award-info":[{"award-number":["EJPRD20-191"]}]},{"DOI":"10.13039\/501100007076","name":"Italian Association for Cancer Research","doi-asserted-by":"publisher","award":["IG 2017 - ID. 19919"],"award-info":[{"award-number":["IG 2017 - ID. 19919"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["1R21CA249378\u201001"],"award-info":[{"award-number":["1R21CA249378\u201001"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Marie Sk\u0142odowska-Curie Actions Postdoctoral Fellowships","award":["DREAM-896947"],"award-info":[{"award-number":["DREAM-896947"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>In the last decade, the sequence-specific transcription factor double homeobox 4 (DUX4) has gone from being an obscure entity to being a key factor in important physiological and pathological processes. We now know that expression of DUX4 is highly regulated and restricted to the early steps of embryonic development, where DUX4 is involved in transcriptional activation of the zygotic genome. While DUX4 is epigenetically silenced in most somatic tissues of healthy humans, its aberrant reactivation is associated with several diseases, including cancer, viral infection and facioscapulohumeral muscular dystrophy (FSHD). DUX4 is also translocated, giving rise to chimeric oncogenic proteins at the basis of sarcoma and leukemia forms. Hence, understanding how DUX4 is regulated and performs its activity could provide relevant information, not only to further our knowledge of human embryonic development regulation, but also to develop therapeutic approaches for the diseases associated with DUX4. Here, we summarize current knowledge on the cellular and molecular processes regulated by DUX4 with a special emphasis on FSHD muscular dystrophy.<\/jats:p>","DOI":"10.3390\/cells10123322","type":"journal-article","created":{"date-parts":[[2021,11,28]],"date-time":"2021-11-28T22:19:16Z","timestamp":1638137956000},"page":"3322","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["DUX4 Role in Normal Physiology and in FSHD Muscular Dystrophy"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4287-8933","authenticated-orcid":false,"given":"Emanuele","family":"Mocciaro","sequence":"first","affiliation":[{"name":"Gene Expression and Muscular Dystrophy Unit, Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, 20132 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6675-2828","authenticated-orcid":false,"given":"Valeria","family":"Runfola","sequence":"additional","affiliation":[{"name":"Gene Expression and Muscular Dystrophy Unit, Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, 20132 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Ghezzi","sequence":"additional","affiliation":[{"name":"Gene Expression and Muscular Dystrophy Unit, Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, 20132 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Pannese","sequence":"additional","affiliation":[{"name":"Gene Expression and Muscular Dystrophy Unit, Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, 20132 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3811-4121","authenticated-orcid":false,"given":"Davide","family":"Gabellini","sequence":"additional","affiliation":[{"name":"Gene Expression and Muscular Dystrophy Unit, Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, 20132 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1038\/ng.3844","article-title":"Conserved roles for murine DUX and human DUX4 in activating cleavage stage genes and MERVL\/HERVL retrotransposons","volume":"49","author":"Hendrickson","year":"2017","journal-title":"Nat. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1038\/ng.3846","article-title":"Conservation and innovation in the DUX4-family gene network","volume":"49","author":"Whiddon","year":"2017","journal-title":"Nat. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1038\/ng.3858","article-title":"DUX-family transcription factors regulate zygotic genome activation in placental mammals","volume":"49","author":"Planet","year":"2017","journal-title":"Nat. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Snider, L., Geng, L.N., Lemmers, R.J.L.F., Kyba, M., Ware, C.B., Nelson, A.M., Tawil, R., Filippova, G.N., van der Maarel, S.M., and Tapscott, S.J. (2010). Facioscapulohumeral Dystrophy: Incomplete Suppression of a Retrotransposed Gene. PLoS Genet., 6.","DOI":"10.1371\/journal.pgen.1001181"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Das, S., and Chadwick, B.P. (2016). Influence of Repressive Histone and DNA Methylation upon D4Z4 Transcription in Non-Myogenic Cells. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0160022"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1038\/s41564-018-0285-5","article-title":"Centrosomal protein TRIM43 restricts herpesvirus infection by regulating nuclear lamina integrity","volume":"4","author":"Full","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e01399-20","DOI":"10.1128\/JVI.01399-20","article-title":"Dissecting Herpes Simplex Virus 1-Induced Host Shutoff at the RNA Level","volume":"95","author":"Friedel","year":"2021","journal-title":"J. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1038\/ng.3535","article-title":"Recurrent DUX4 fusions in B cell acute lymphoblastic leukemia of adolescents and young adults","volume":"48","author":"Yasuda","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"11790","DOI":"10.1038\/ncomms11790","article-title":"Identification of ETV6-RUNX1-like and DUX4-rearranged subtypes in paediatric B-cell precursor acute lymphoblastic leukaemia","volume":"7","author":"Henningsson","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1038\/ng.3691","article-title":"Deregulation of DUX4 and ERG in acute lymphoblastic leukemia","volume":"48","author":"Zhang","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_11","first-page":"236","article-title":"Undifferentiated round cell sarcomas with CIC-DUX4 gene fusion: Expanding the clinical spectrum","volume":"52","author":"Brodowicz","year":"2020","journal-title":"Pathology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1016\/j.stem.2018.10.011","article-title":"Oncogenic Amplification of Zygotic Dux Factors in Regenerating p53-Deficient Muscle Stem Cells Defines a Molecular Cancer Subtype","volume":"23","author":"Preussner","year":"2018","journal-title":"Cell Stem Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1016\/j.devcel.2019.06.011","article-title":"DUX4 Suppresses MHC Class I to Promote Cancer Immune Evasion and Resistance to Checkpoint Blockade","volume":"50","author":"Chew","year":"2019","journal-title":"Dev. Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1016\/j.celrep.2019.09.087","article-title":"NFE2L3 Controls Colon Cancer Cell Growth through Regulation of DUX4, a CDK1 Inhibitor","volume":"29","author":"Bury","year":"2019","journal-title":"Cell Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1146\/annurev-genom-083118-014933","article-title":"The Genetics and Epigenetics of Facioscapulohumeral Muscular Dystrophy","volume":"20","author":"Himeda","year":"2019","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1111\/cge.13726","article-title":"Consequences of epigenetic derepression in facioscapulohumeral muscular dystrophy","volume":"97","author":"Greco","year":"2020","journal-title":"Clin. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1086\/519311","article-title":"Evolutionary Conservation of a Coding Function for D4Z4, the Tandem DNA Repeat Mutated in Facioscapulohumeral Muscular Dystrophy","volume":"81","author":"Clapp","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Leidenroth, A., and Hewitt, J.E. (2010). A family history of DUX4: Phylogenetic analysis of DUXA, B, C and Duxbl reveals the ancestral DUXgene. BMC Evol. Biol., 10.","DOI":"10.1186\/1471-2148-10-364"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1146\/annurev.bi.63.070194.002415","article-title":"Homeodomain Proteins","volume":"63","author":"Gehring","year":"2003","journal-title":"Annu. Rev. Biochem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1016\/j.bbrc.2018.10.056","article-title":"Structural basis for multiple gene regulation by human DUX4","volume":"505","author":"Li","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2955","DOI":"10.1016\/j.celrep.2018.11.060","article-title":"Crystal Structure of the Double Homeodomain of DUX4 in Complex with DNA","volume":"25","author":"Lee","year":"2018","journal-title":"Cell Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Corona, E.D., Jacquelin, D., Gatica, L., and Rosa, A.L. (2013). Multiple protein domains contribute to nuclear import and cell toxicity of DUX4, a candidate pathogenic protein for facioscapulohumeral muscular dystrophy. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0075614"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4573","DOI":"10.1096\/fj.201902696","article-title":"DNA aptamers against the DUX4 protein reveal novel therapeutic implications for FSHD","volume":"34","author":"Klingler","year":"2020","journal-title":"FASEB J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s13395-016-0080-z","article-title":"DNA-binding sequence specificity of DUX4","volume":"6","author":"Zhang","year":"2016","journal-title":"Skelet. Muscle"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"dev161471","DOI":"10.1242\/dev.161471","article-title":"The maternal-to-zygotic transition revisited","volume":"146","author":"Vastenhouw","year":"2019","journal-title":"Development"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.stem.2015.01.005","article-title":"Dynamic transcription of distinct classes of endogenous retroviral elements marks specific populations of early human embryonic cells","volume":"16","author":"Lu","year":"2015","journal-title":"Cell Stem Cell"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Vuoristo, S., Hyd\u00e9n-Granskog, C., Yoshihara, M., Gawriyski, L., Damdimopoulos, A., Bhagat, S., Hashimoto, K., Krjut\u0161kov, K., Ezer, S., and Paluoja, P. (2019). DUX4 regulates oocyte to embryo transition in human. bioRxiv, 732289.","DOI":"10.1101\/732289"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1038\/s41588-019-0418-7","article-title":"Loss of DUX causes minor defects in zygotic genome activation and is compatible with mouse development","volume":"51","author":"Chen","year":"2019","journal-title":"Nat. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1038\/s41422-019-0238-4","article-title":"Precise temporal regulation of Dux is important for embryo development","volume":"29","author":"Guo","year":"2019","journal-title":"Cell Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"dev177725","DOI":"10.1242\/dev.177725","article-title":"DUX is a non-essential synchronizer of zygotic genome activation","volume":"147","author":"Verp","year":"2020","journal-title":"Development"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1093\/biolre\/ioaa179","article-title":"Dux facilitates post-implantation development, but is not essential for zygotic genome activation","volume":"104","author":"Bosnakovski","year":"2021","journal-title":"Biol. Reprod."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e54756","DOI":"10.7554\/eLife.54756","article-title":"ATR expands embryonic stem cell fate potential in response to replication stress","volume":"9","author":"Atashpaz","year":"2020","journal-title":"Elife"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1038\/s41588-021-00893-0","article-title":"p53 convergently activates Dux\/DUX4 in embryonic stem cells and in facioscapulohumeral muscular dystrophy cell models","volume":"53","author":"Grow","year":"2021","journal-title":"Nat. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.cell.2018.05.043","article-title":"A LINE1-Nucleolin partnership regulates early development and ES cell identity HHS Public Access","volume":"174","author":"Percharde","year":"2018","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2262","DOI":"10.1093\/emboj\/16.9.2262","article-title":"An early and massive wave of germinal cell apoptosis is required for the development of functional spermatogenesis","volume":"16","author":"Rodriguez","year":"1997","journal-title":"EMBO J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1098\/rstb.2009.0124","article-title":"Male germ cell apoptosis: Regulation and biology","volume":"365","author":"Shaha","year":"2010","journal-title":"Philos. Trans. R. Soc. Lond. B. Biol. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5335","DOI":"10.4049\/jimmunol.179.8.5335","article-title":"Expression profiling of immature thymocytes revealed a novel homeobox gene that regulates double-negative thymocyte development","volume":"179","author":"Kawazu","year":"2007","journal-title":"J. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1084\/jem.20181444","article-title":"The transcription factor Duxbl mediates elimination of pre-T cells that fail \u03b2-selection","volume":"216","author":"Klein","year":"2019","journal-title":"J. Exp. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.devcel.2011.11.013","article-title":"DUX4 Activates Germline Genes, Retroelements, and Immune Mediators: Implications for Facioscapulohumeral Dystrophy","volume":"22","author":"Geng","year":"2012","journal-title":"Dev. Cell"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Young, J.M., Whiddon, J.L., Yao, Z., Kasinathan, B., Snider, L., Geng, L.N., Balog, J., Tawil, R., van der Maarel, S.M., and Tapscott, S.J. (2013). DUX4 Binding to Retroelements Creates Promoters That Are Active in FSHD Muscle and Testis. PLoS Genet., 9.","DOI":"10.1371\/journal.pgen.1003947"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5901","DOI":"10.1093\/hmg\/ddv315","article-title":"Endogenous DUX4 expression in FSHD myotubes is sufficient to cause cell death and disrupts RNA splicing and cell migration pathways","volume":"24","author":"Rickard","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_43","unstructured":"Campbell, A.E., Dyle, M.C., Calviello, L., Matheny, T., Cortazar, M.A., Forman, T., Fu, R., Gillen, A.E., Floor, S.N., and Jagannathan, S. (2021). The myopathic transcription factor DUX4 induces the production of truncated RNA-binding proteins in human muscle cells. bioRxiv."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1177\/1087057116651868","article-title":"Transcriptional Inhibitors Identified in a 160,000-Compound Small-Molecule DUX4 Viability Screen","volume":"21","author":"Choi","year":"2016","journal-title":"J. Biomol. Screen."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-017-01200-4","article-title":"PAX7 target genes are globally repressed in facioscapulohumeral muscular dystrophy skeletal muscle","volume":"8","author":"Banerji","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/j.cell.2012.03.035","article-title":"A long ncRNA links copy number variation to a polycomb\/trithorax epigenetic switch in fshd muscular dystrophy","volume":"149","author":"Cabianca","year":"2012","journal-title":"Cell"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Sharma, V., Harafuji, N., Belayew, A., and Chen, Y.W. (2013). DUX4 Differentially Regulates Transcriptomes of Human Rhabdomyosarcoma and Mouse C2C12 Cells. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0064691"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5342","DOI":"10.1093\/hmg\/ddu251","article-title":"DUX4-induced gene expression is the major molecular signature in FSHD skeletal muscle","volume":"23","author":"Yao","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_49","first-page":"4419","article-title":"Model systems of DUX4 expression recapitulate the transcriptional profile of FSHD cells","volume":"25","author":"Jagannathan","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e13695","DOI":"10.15252\/emmm.202013695","article-title":"Pathomechanisms and biomarkers in facioscapulohumeral muscular dystrophy: Roles of DUX4 and PAX7","volume":"13","author":"Banerji","year":"2021","journal-title":"EMBO Mol. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2909","DOI":"10.1093\/hmg\/ddg323","article-title":"Testing the position-effect variegation hypothesis for facioscapulohumeral muscular dystrophy by analysis of histone modification and gene expression in subtelomeric 4q","volume":"12","author":"Jiang","year":"2003","journal-title":"Hum. Mol. Genet."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1002\/humu.24171","article-title":"Relationship of DUX4 and target gene expression in FSHD myocytes","volume":"42","author":"Chau","year":"2021","journal-title":"Hum. Mutat."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1016\/j.celrep.2019.10.025","article-title":"DUX4-Induced Histone Variants H3.X and H3.Y Mark DUX4 Target Genes for Expression","volume":"29","author":"Resnick","year":"2019","journal-title":"Cell Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3997","DOI":"10.1093\/hmg\/ddz242","article-title":"DUX4-induced bidirectional HSATII satellite repeat transcripts form intranuclear double-stranded RNA foci in human cell models of FSHD","volume":"28","author":"Shadle","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Sidlauskaite, E., Le Gall, L., Mariot, V., and Dumonceaux, J. (2020). DUX4 expression in FSHD muscles: Focus on its mRNA regulation. J. Pers. Med., 10.","DOI":"10.3390\/jpm10030073"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1016\/j.molmed.2021.03.008","article-title":"Control of DUX4 Expression in Facioscapulohumeral Muscular Dystrophy and Cancer","volume":"27","author":"Karpukhina","year":"2021","journal-title":"Trends Mol. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1212\/WNL.0000000000000797","article-title":"EPopulation-based incidence and prevalence of facioscapulohumeral dystrophy","volume":"83","author":"Deenen","year":"2014","journal-title":"Neurology"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Padberg, G.W. (2010). Facioscapulohumeral muscular dystrophy. International Neurology, Wiley-Blackwell.","DOI":"10.1002\/9781444317008.ch59"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.bbadis.2014.05.021","article-title":"Facioscapulohumeral muscular dystrophy","volume":"1852","author":"Sacconi","year":"2015","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/mus.20522","article-title":"Facioscapulohumeral muscular dystrophy","volume":"34","author":"Tawil","year":"2006","journal-title":"Muscle Nerve"},{"key":"ref_61","first-page":"1916","article-title":"Facioscapulohumeral Muscular Dystrophy","volume":"22","author":"Statland","year":"2016","journal-title":"Continuum"},{"key":"ref_62","first-page":"1662","article-title":"Facioscapulohumeral Muscular Dystrophies","volume":"25","author":"Wagner","year":"2019","journal-title":"Continuum"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1126\/science.1189044","article-title":"A unifying genetic model for facioscapulohumeral muscular dystrophy","volume":"329","author":"Lemmers","year":"2010","journal-title":"Science"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1086\/521986","article-title":"Specific Sequence Variations within the 4q35 Region Are Associated with Facioscapulohumeral Muscular Dystrophy","volume":"81","author":"Lemmers","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Lim, K.R.Q., Nguyen, Q., and Yokota, T. (2020). Dux4 signalling in the pathogenesis of facioscapulohumeral muscular dystrophy. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21030729"},{"key":"ref_66","first-page":"1","article-title":"Facioscapulohumeral muscular dystrophy: Genetics, gene activation and downstream signalling with regard to recent therapeutic approaches: An update","volume":"16","author":"Kaiser","year":"2021","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2766","DOI":"10.1038\/emboj.2008.201","article-title":"An isogenetic myoblast expression screen identifies DUX4-mediated FSHD-associated molecular pathologies","volume":"27","author":"Bosnakovski","year":"2008","journal-title":"EMBO J."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.freeradbiomed.2016.08.007","article-title":"DUX4-induced constitutive DNA damage and oxidative stress contribute to aberrant differentiation of myoblasts from FSHD patients","volume":"99","author":"Dmitriev","year":"2016","journal-title":"Free Radic. Biol. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1111\/j.1582-4934.2008.00368.x","article-title":"Myoblasts from affected and non-affected FSHD muscles exhibit morphological differentiation defects","volume":"14","author":"Barro","year":"2010","journal-title":"J. Cell. Mol. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-018-35150-8","article-title":"Low level DUX4 expression disrupts myogenesis through deregulation of myogenic gene expression","volume":"8","author":"Bosnakovski","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Vanderplanck, C., Ansseau, E., Charron, S., Stricwant, N., Tassin, A., Laoudj-Chenivesse, D., Wilton, S.D., Copp\u00e9e, F., and Belayew, A. (2011). The FSHD atrophic myotube phenotype is caused by DUX4 expression. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0026820"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e04996","DOI":"10.7554\/eLife.04996","article-title":"A feedback loop between nonsense-mediated decay and the retrogene DUX4 in facioscapulohumeral muscular dystrophy","volume":"4","author":"Feng","year":"2015","journal-title":"Elife"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Shadle, S.C., Zhong, J.W., Campbell, A.E., Conerly, M.L., Jagannathan, S., Wong, C.J., Morello, T.D., van der Maarel, S.M., and Tapscott, S.J. (2017). DUX4-induced dsRNA and MYC mRNA stabilization activate apoptotic pathways in human cell models of facioscapulohumeral dystrophy. PLoS Genet., 13.","DOI":"10.1371\/journal.pgen.1006658"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/j.nmd.2007.04.002","article-title":"The DUX4 gene at the FSHD1A locus encodes a pro-apoptotic protein","volume":"17","author":"Kowaljow","year":"2007","journal-title":"Neuromuscul. Disord."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.bbrc.2014.05.126","article-title":"Erratum: Dux4 induces cell cycle arrest at G1 phase through up regulation of p21 expression","volume":"450","author":"Xu","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1007\/s11910-016-0667-0","article-title":"Facioscapulohumeral Dystrophy","volume":"16","author":"Wang","year":"2016","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"S56","DOI":"10.1002\/mus.880181312","article-title":"Inflammatory response in facioscapulohumeral muscular dystrophy (FSHD): Immunocytochemical and genetic analyses","volume":"18","author":"Arahata","year":"1995","journal-title":"Muscle Nerve"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1093\/hmg\/ddy364","article-title":"MRI-informed muscle biopsies correlate MRI with pathology and DUX4 target gene expression in FSHD","volume":"28","author":"Wang","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1093\/hmg\/ddaa031","article-title":"Longitudinal measures of RNA expression and disease activity in FSHD muscle biopsies","volume":"29","author":"Wong","year":"2020","journal-title":"Hum. Mol. Genet."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2465","DOI":"10.1172\/JCI133303","article-title":"Transcriptional and cytopathological hallmarks of FSHD in chronic DUX4-expressing mice","volume":"130","author":"Bosnakovski","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2285","DOI":"10.1093\/hmg\/ddaa053","article-title":"DUX4 expressing immortalized FSHD lymphoblastoid cells express genes elevated in FSHD muscle biopsies, correlating with the early stages of inflammation","volume":"29","author":"Banerji","year":"2020","journal-title":"Hum. Mol. Genet."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2094","DOI":"10.1002\/art.41427","article-title":"Antibodies Against Three Novel Peptides in Early Axial Spondyloarthritis Patients From Two Independent Cohorts","volume":"72","author":"Quaden","year":"2020","journal-title":"Arthritis Rheumatol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e141908","DOI":"10.1172\/JCI141908","article-title":"ETV4 and ETV5 drive synovial sarcoma through cell cycle and DUX4 embryonic pathway control","volume":"131","author":"DeSalvo","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.1093\/hmg\/ddl136","article-title":"Fusion between CIC and DUX4 up-regulates PEA3 family genes in Ewing-like sarcomas with t(4;19)(q35;q13) translocation","volume":"15","author":"Yamazaki","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.ebiom.2016.04.038","article-title":"Genomic Profiling of Adult and Pediatric B-cell Acute Lymphoblastic Leukemia","volume":"8","author":"Liu","year":"2016","journal-title":"EBioMedicine"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1038\/s12276-020-0411-3","article-title":"Regulation and function of capicua in mammals","volume":"52","author":"Lee","year":"2020","journal-title":"Exp. Mol. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"5161","DOI":"10.1093\/nar\/gkw141","article-title":"DUX4 recruits p300\/CBP through its C-terminus and induces global H3K27 acetylation changes","volume":"44","author":"Choi","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1016\/S0092-8674(00)82001-2","article-title":"The Transcriptional Coactivators p300 and CBP Are Histone Acetyltransferases","volume":"87","author":"Ogryzko","year":"1996","journal-title":"Cell"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.expneurol.2008.07.022","article-title":"DUX4c, an FSHD candidate gene, interferes with myogenic regulators and abolishes myoblast differentiation","volume":"214","author":"Bosnakovski","year":"2008","journal-title":"Exp. Neurol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"eaaw7781","DOI":"10.1126\/sciadv.aaw7781","article-title":"A novel P300 inhibitor reverses DUX4-mediated global histone H3 hyperacetylation, target gene expression, and cell death","volume":"5","author":"Bosnakovski","year":"2019","journal-title":"Sci. Adv."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Ansseau, E., Eidahl, J.O., Lancelot, C., Tassin, A., Matteotti, C., Yip, C., Liu, J., Leroy, B., Hubeau, C., and Gerbaux, C. (2016). Homologous Transcription Factors DUX4 and DUX4c Associate with Cytoplasmic Proteins during Muscle Differentiation. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0146893"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s00401-012-1057-6","article-title":"Desminopathies: Pathology and mechanisms","volume":"125","author":"Clemen","year":"2013","journal-title":"Acta Neuropathol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1186\/s13054-016-1563-3","article-title":"Skeletal muscle quality as assessed by CT-derived skeletal muscle density is associated with 6-month mortality in mechanically ventilated critically ill patients","volume":"20","author":"Looijaard","year":"2016","journal-title":"Crit. Care"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"eaaw7099","DOI":"10.1126\/sciadv.aaw7099","article-title":"Identification of the hyaluronic acid pathway as a therapeutic target for facioscapulohumeral muscular dystrophy","volume":"5","author":"DeSimone","year":"2019","journal-title":"Sci. Adv."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s13395-017-0134-x","article-title":"BET bromodomain inhibitors and agonists of the beta-2 adrenergic receptor identified in screens for compounds that inhibit DUX4 expression in FSHD muscle cells","volume":"7","author":"Campbell","year":"2017","journal-title":"Skelet. Muscle"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1","DOI":"10.7554\/eLife.41740","article-title":"Quantitative proteomics reveals key roles for post-transcriptional gene regulation in the molecular pathology of facioscapulohumeral muscular dystrophy","volume":"8","author":"Jagannathan","year":"2019","journal-title":"Elife"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2505","DOI":"10.1016\/j.celrep.2019.10.082","article-title":"Dynamic Transcriptome-Proteome Correlation Networks Reveal Human Myeloid Differentiation and Neutrophil-Specific Programming","volume":"29","author":"Hoogendijk","year":"2019","journal-title":"Cell Rep."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"R25","DOI":"10.1186\/gb-2012-13-4-r25","article-title":"Regulation of transcriptome, translation, and proteome in response to environmental stress in fission yeast","volume":"13","author":"Lackner","year":"2012","journal-title":"Genome Biol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1038\/msb.2011.48","article-title":"A dynamic model of proteome changes reveals new roles for transcript alteration in yeast","volume":"7","author":"Lee","year":"2011","journal-title":"Mol. Syst. Biol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1038\/s41580-019-0126-2","article-title":"Quality and quantity control of gene expression by nonsense-mediated mRNA decay","volume":"20","author":"Kurosaki","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1016\/j.molcel.2011.06.031","article-title":"RNA Homeostasis Governed by Cell Type-Specific and Branched Feedback Loops Acting on NMD","volume":"43","author":"Huang","year":"2011","journal-title":"Mol. Cell"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1002\/acn3.158","article-title":"Expression of FSHD-related DUX4-FL alters proteostasis and induces TDP-43 aggregation","volume":"2","author":"Homma","year":"2015","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1016\/j.celrep.2013.08.015","article-title":"Heterochromatin Reorganization during Early Mouse Development Requires a Single-Stranded Noncoding Transcript","volume":"4","author":"Casanova","year":"2013","journal-title":"Cell Rep."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"40038","DOI":"10.1074\/jbc.M111.266361","article-title":"Overexpression of the c-myc oncogene inhibits nonsense-mediated RNA decay in B lymphocytes","volume":"286","author":"Wang","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s00401-007-0237-2","article-title":"Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: Consensus of the Consortium for Frontotemporal Lobar Degeneration","volume":"114","author":"Cairns","year":"2007","journal-title":"Acta Neuropathol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/j.bbrc.2006.10.093","article-title":"TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis","volume":"351","author":"Arai","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.neuron.2013.07.033","article-title":"Converging mechanisms in als and FTD: Disrupted RNA and protein homeostasis","volume":"79","author":"Ling","year":"2013","journal-title":"Neuron"},{"key":"ref_108","first-page":"E1121","article-title":"Partial loss of TDP-43 function causes phenotypes of amyotrophic lateral sclerosis","volume":"111","author":"Yang","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"905612","DOI":"10.1155\/2010\/905612","article-title":"Interaction among Skeletal Muscle Metabolic Energy Systems during Intense Exercise","volume":"2010","author":"Baker","year":"2010","journal-title":"J. Nutr. Metab."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1007\/s11910-010-0096-4","article-title":"Diagnostic algorithm for metabolic myopathies","volume":"10","author":"Berardo","year":"2010","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1055\/s-0035-1558973","article-title":"Metabolic myopathies","volume":"Volume 35","author":"Adler","year":"2015","journal-title":"Seminars in Neurology"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1146\/annurev-physiol-020518-114310","article-title":"Maintenance of Skeletal Muscle Mitochondria in Health, Exercise, and Aging","volume":"81","author":"Hood","year":"2019","journal-title":"Annu. Rev. Physiol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1038\/emboj.2010.60","article-title":"Mitochondrial fission and remodelling contributes to muscle atrophy","volume":"29","author":"Romanello","year":"2010","journal-title":"EMBO J."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1515\/hsz-2012-0247","article-title":"Mitochondrial pathways in sarcopenia of aging and disuse muscle atrophy","volume":"394","author":"Calvani","year":"2013","journal-title":"Biol. Chem."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1016\/j.cmet.2018.07.012","article-title":"Perturbed Redox Signaling Exacerbates a Mitochondrial Myopathy","volume":"28","author":"Dogan","year":"2018","journal-title":"Cell Metab."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1016\/j.freeradbiomed.2012.06.041","article-title":"Functional muscle impairment in facioscapulohumeral muscular dystrophy is correlated with oxidative stress and mitochondrial dysfunction","volume":"53","author":"Turki","year":"2012","journal-title":"Free Radic. Biol. Med."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Heher, P., Ganassi, M., Weidinger, A., Engquist, E., Pruller, J., Nguyen, T., Tassin, A., Decl\u00e8ves, A., Mamchaoui, K., and Grillari, J. (2021). Interplay between mitochondria and reactive oxygen and nitrogen species in metabolic adaptation to hypoxia in facioscapulohumeral muscular dystrophy: Potential therapeutic targets. bioRxiv.","DOI":"10.1101\/2021.09.08.459509"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1002\/nbm.1494","article-title":"Only fat infiltrated muscles in resting lower leg of FSHD patients show disturbed energy metabolism","volume":"23","author":"Kan","year":"2010","journal-title":"NMR Biomed."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.cca.2017.12.036","article-title":"Perturbation of muscle metabolism in patients with muscular dystrophy in early or acute phase of disease: In vitro, high resolution NMR spectroscopy based analysis","volume":"478","author":"Srivastava","year":"2018","journal-title":"Clin. Chim. Acta"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/S0960-8966(02)00284-5","article-title":"Facioscapulohumeral muscular dystrophy (FSHD) myoblasts demonstrate increased susceptibility to oxidative stress","volume":"13","author":"Winokur","year":"2003","journal-title":"Neuromuscul. Disord."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"20140797","DOI":"10.1098\/rsif.2014.0797","article-title":"\u03b2-catenin is central to DUX4-driven network rewiring in facioscapulohumeral muscular dystrophy","volume":"12","author":"Banerji","year":"2015","journal-title":"J. R. Soc. Interface"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"eaay0271","DOI":"10.1126\/scitranslmed.aay0271","article-title":"Applying genome-wide CRISPR-Cas9 screens for therapeutic discovery in facioscapulohumeral muscular dystrophy","volume":"12","author":"Lek","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"C817","DOI":"10.1152\/ajpcell.00139.2004","article-title":"Calcium, ATP, and ROS: A mitochondrial love-hate triangle","volume":"287","author":"Brookes","year":"2004","journal-title":"Am. J. Physiol. -Cell Physiol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/B978-0-12-381510-1.00069-7","article-title":"Facioscapulohumeral muscular dystrophy: Unraveling the mysteries of a complex epigenetic disease","volume":"2","author":"Himeda","year":"2012","journal-title":"Muscle"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/s41586-019-1667-4","article-title":"The ADP\/ATP translocase drives mitophagy independent of nucleotide exchange","volume":"575","author":"Hoshino","year":"2019","journal-title":"Nature"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/S0092-8674(02)00826-7","article-title":"Inappropriate gene activation in FSHD: A repressor complex binds a chromosomal repeat deleted in dystrophic muscle","volume":"110","author":"Gabellini","year":"2002","journal-title":"Cell"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1111\/j.1600-0404.2006.00724.x","article-title":"RAGE-NF-\u03baB pathway activation in response to oxidative stress in facioscapulohumeral muscular dystrophy","volume":"115","author":"Macaione","year":"2007","journal-title":"Acta Neurol. Scand."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1007\/s00109-004-0583-7","article-title":"Increased levels of adenine nucleotide translocator 1 protein and response to oxidative stress are early events in facioscapulohumeral muscular dystrophy muscle","volume":"83","author":"Carnac","year":"2005","journal-title":"J. Mol. Med."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1038\/ejhg.2009.62","article-title":"Comprehensive expression analysis of FSHD candidate genes at the mRNA and protein level","volume":"17","author":"Klooster","year":"2009","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1038\/ejhg.2009.183","article-title":"Analysis of allele-specific RNA transcription in FSHD by RNA-DNA FISH in single myonuclei","volume":"18","author":"Masny","year":"2010","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"8227","DOI":"10.1093\/nar\/gkv721","article-title":"ZNF555 protein binds to transcriptional activator site of 4qA allele and ANT1: Potential implication in Facioscapulohumeral dystrophy","volume":"43","author":"Kim","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Wang, X., Middleton, F.A., Tawil, R., and Chen, X.J. (2020). Cytosolic Adaptation to Mitochondrial Precursor Overaccumulation Stress Induces Progressive Muscle Wasting. bioRxiv, 733097.","DOI":"10.1101\/733097"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1093\/hmg\/ddy405","article-title":"Dynamic transcriptomic analysis reveals suppression of PGC1\u03b1\/ERR\u03b1 drives perturbed myogenesis in facioscapulohumeral muscular dystrophy","volume":"28","author":"Banerji","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Bittel, A.J., Sreetama, S.C., Bittel, D.C., Horn, A., Novak, J.S., Yokota, T., Zhang, A., Maruyama, R., Lim, K.R.Q., and Jaiswal, J.K. (2020). Membrane Repair Deficit in Facioscapulohumeral Muscular Dystrophy. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21155575"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"2895","DOI":"10.1093\/hmg\/ddg327","article-title":"Expression profiling of FSHD muscle supports a defect in specific stages of myogenic differentiation","volume":"12","author":"Winokur","year":"2003","journal-title":"Hum. Mol. Genet."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"5303","DOI":"10.1002\/pmic.200600056","article-title":"Parallel protein and transcript profiles of FSHD patient muscles correlate to the D4Z4 arrangement and reveal a common impairment of slow to fast fibre differentiation and a general deregulation of MyoD-dependent genes","volume":"6","author":"Celegato","year":"2006","journal-title":"Proteomics"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"4206","DOI":"10.1093\/hmg\/ddt272","article-title":"Dysregulation of 4q35- and muscle-specific genes in fetuses with a short D4Z4 array linked to facio-scapulo-humeral dystrophy","volume":"22","author":"Broucqsault","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"2845","DOI":"10.1242\/dev.069088","article-title":"Satellite cells are essential for skeletal muscle regeneration: The cell on the edge returns centre stage","volume":"139","author":"Relaix","year":"2012","journal-title":"Development"},{"key":"ref_139","first-page":"779","article-title":"Muscle regeneration: Cellular and molecular events","volume":"23","author":"Karalaki","year":"2009","journal-title":"In Vivo"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"16474","DOI":"10.1073\/pnas.1307680110","article-title":"Pax7 is critical for the normal function of satellite cells in adult skeletal muscle","volume":"110","author":"Jones","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"2124","DOI":"10.1093\/hmg\/ddaa079","article-title":"PAX7 target gene repression associates with FSHD progression and pathology over 1 year","volume":"29","author":"Banerji","year":"2020","journal-title":"Hum. Mol. Genet."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"2224","DOI":"10.1093\/hmg\/ddz043","article-title":"PAX7 target gene repression is a superior FSHD biomarker than DUX4 target gene activation, associating with pathological severity and identifying FSHD at the single-cell level","volume":"28","author":"Banerji","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s13395-017-0130-1","article-title":"Expression patterns of FSHD-causing DUX4 and myogenic transcription factors PAX3 and PAX7 are spatially distinct in differentiating human stem cell cultures","volume":"7","author":"Haynes","year":"2017","journal-title":"Skelet. Muscle"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"e11405","DOI":"10.7554\/eLife.11405","article-title":"Ret function in muscle stem cells points to tyrosine kinase inhibitor therapy for facioscapulohumeral muscular dystrophy","volume":"5","author":"Moyle","year":"2016","journal-title":"Elife"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/ncb2015","article-title":"Muscle injury activates resident fibro\/adipogenic progenitors that facilitate myogenesis","volume":"12","author":"Joe","year":"2010","journal-title":"Nat. Cell Biol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"2559","DOI":"10.1007\/s00018-019-03093-6","article-title":"Adult stem cells at work: Regenerating skeletal muscle","volume":"76","author":"Schmidt","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1038\/s41467-017-00730-1","article-title":"Muscle pathology from stochastic low level DUX4 expression in an FSHD mouse model","volume":"8","author":"Bosnakovski","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_148","first-page":"4577","article-title":"Mouse Dux is myotoxic and shares partial functional homology with its human paralog DUX4","volume":"25","author":"Eidahl","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.molmed.2015.02.011","article-title":"Emerging preclinical animal models for FSHD","volume":"21","author":"Lek","year":"2015","journal-title":"Trends Mol. Med."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"dmm046904","DOI":"10.1242\/dmm.046904","article-title":"Cellular and animal models for facioscapulohumeral muscular dystrophy","volume":"13","author":"DeSimone","year":"2020","journal-title":"Dis. Model. Mech."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1016\/j.celrep.2014.07.056","article-title":"Dominant lethal pathologies in male mice engineered to contain an X-linked DUX4 transgene","volume":"8","author":"Dandapat","year":"2014","journal-title":"Cell Rep."},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Jones, T., and Jones, P. (2018). A cre-inducible DUX4 transgenic mouse model for investigating facioscapulohumeral muscular dystrophy. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0192657"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"e123538","DOI":"10.1172\/jci.insight.123538","article-title":"AAV-mediated follistatin gene therapy improves functional outcomes in the TIC-DUX4 mouse model of FSHD","volume":"3","author":"Giesige","year":"2018","journal-title":"JCI insight"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s13395-020-00227-4","article-title":"Transgenic mice expressing tunable levels of DUX4 develop characteristic facioscapulohumeral muscular dystrophy-like pathophysiology ranging in severity","volume":"10","author":"Jones","year":"2020","journal-title":"Skelet. Muscle"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1038\/mt.2016.111","article-title":"Morpholino-mediated Knockdown of DUX4 Toward Facioscapulohumeral Muscular Dystrophy Therapeutics","volume":"24","author":"Chen","year":"2016","journal-title":"Mol. Ther."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"113011","DOI":"10.1016\/j.expneurol.2019.113011","article-title":"Muscle xenografts reproduce key molecular features of facioscapulohumeral muscular dystrophy","volume":"320","author":"Mueller","year":"2019","journal-title":"Exp. Neurol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1124\/jpet.119.259663","article-title":"Clinically Advanced p38 Inhibitors Suppress DUX4 Expression in Cellular and Animal Models of Facioscapulohumeral Muscular Dystrophy","volume":"370","author":"Oliva","year":"2019","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s13395-016-0078-6","article-title":"Neuromuscular electrical stimulation promotes development in mice of mature human muscle from immortalized human myoblasts","volume":"6","author":"Sakellariou","year":"2016","journal-title":"Skelet. Muscle"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"4817","DOI":"10.1093\/hmg\/ddv206","article-title":"DICER\/AGO-dependent epigenetic silencing of D4Z4 repeats enhanced by exogenous siRNA suggests mechanisms and therapies for FSHD","volume":"24","author":"Lim","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1038\/mt.2015.200","article-title":"CRISPR\/dCas9-mediated transcriptional inhibition ameliorates the epigenetic dysregulation at D4Z4 and represses DUX4-fl in FSH muscular dystrophy","volume":"24","author":"Himeda","year":"2016","journal-title":"Mol. Ther."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1016\/j.ymthe.2018.04.019","article-title":"Identification of Epigenetic Regulators of DUX4-fl for Targeted Therapy of Facioscapulohumeral Muscular Dystrophy","volume":"26","author":"Himeda","year":"2018","journal-title":"Mol. Ther."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1136\/jmedgenet-2019-106402","article-title":"Intronic SMCHD1 variants in FSHD: Testing the potential for CRISPR-Cas9 genome editing","volume":"56","author":"Goossens","year":"2019","journal-title":"J. Med. Genet."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.omtm.2020.12.001","article-title":"Targeted epigenetic repression by CRISPR\/dSaCas9 suppresses pathogenic DUX4-fl expression in FSHD","volume":"20","author":"Himeda","year":"2021","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Joubert, R., Mariot, V., Charpentier, M., Concordet, J.P., and Dumonceaux, J. (2020). Gene Editing Targeting the DUX4 Polyadenylation Signal: A Therapy for FSHD?. J. Pers. Med., 11.","DOI":"10.3390\/jpm11010007"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"12598","DOI":"10.1038\/s41598-021-92096-0","article-title":"CRISPR mediated targeting of DUX4 distal regulatory element represses DUX4 target genes dysregulated in Facioscapulohumeral muscular dystrophy","volume":"11","author":"Das","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.freeradbiomed.2014.09.014","article-title":"Effects of vitamin C, vitamin E, zinc gluconate, and selenomethionine supplementation on muscle function and oxidative stress biomarkers in patients with facioscapulohumeral dystrophy: A double-blind randomized controlled clinical trial","volume":"81","author":"Passerieux","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/j.nmd.2006.08.005","article-title":"No effect of folic acid and methionine supplementation on D4Z4 methylation in patients with facioscapulohumeral muscular dystrophy","volume":"16","author":"Wohlgemuth","year":"2006","journal-title":"Neuromuscul. Disord."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1212\/WNL.48.1.46","article-title":"A pilot trial of prednisone in facioscapulohumeral muscular dystrophy","volume":"48","author":"Tawil","year":"1997","journal-title":"Neurology"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1002\/ana.21338","article-title":"A phase I\/II trial of MYO-029 in adult subjects with muscular dystrophy","volume":"63","author":"Wagner","year":"2008","journal-title":"Ann. Neurol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1172\/JCI89401","article-title":"Estrogens enhance myoblast differentiation in facioscapulohumeral muscular dystrophy by antagonizing DUX4 activity","volume":"127","author":"Teveroni","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1016\/j.apmr.2008.12.027","article-title":"Periodic Salbutamol in Facioscapulohumeral Muscular Dystrophy: A Randomized Controlled Trial","volume":"90","author":"Payan","year":"2009","journal-title":"Arch. Phys. Med. Rehabil."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1212\/WNL.57.8.1434","article-title":"Randomized, double-blind, placebo-controlled trial of albuterol in facioscapulohumeral dystrophy","volume":"57","author":"Kissel","year":"2001","journal-title":"Neurology"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1002\/mus.10527","article-title":"Creatine monohydrate supplementation does not increase muscle strength, lean body mass, or muscle phosphocreatine in patients with myotonic dystrophy type 1","volume":"29","author":"Tarnopolsky","year":"2004","journal-title":"Muscle Nerve"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"441","DOI":"10.3233\/JND-200554","article-title":"Current Therapeutic Approaches in FSHD","volume":"8","author":"Wang","year":"2021","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"281","DOI":"10.3389\/fphar.2021.642858","article-title":"Genetic Approaches for the Treatment of Facioscapulohumeral Muscular Dystrophy","volume":"12","author":"Lim","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.molmed.2020.09.008","article-title":"Therapeutic Approaches in Facioscapulohumeral Muscular Dystrophy","volume":"27","author":"Cohen","year":"2021","journal-title":"Trends Mol. Med."},{"key":"ref_177","doi-asserted-by":"crossref","unstructured":"Le Gall, L., Sidlauskaite, E., Mariot, V., and Dumonceaux, J. (2020). Therapeutic Strategies Targeting DUX4 in FSHD. J. Clin. Med., 9.","DOI":"10.3390\/jcm9092886"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"1912","DOI":"10.1016\/j.celrep.2018.10.044","article-title":"Smchd1 Targeting to the Inactive X Is Dependent on the Xist-HnrnpK-PRC1 Pathway","volume":"25","author":"Jansz","year":"2018","journal-title":"Cell Rep."},{"key":"ref_179","first-page":"1","article-title":"PRC1 collaborates with SMCHD1 to fold the X-chromosome and spread Xist RNA between chromosome compartments","volume":"10","author":"Wang","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_180","first-page":"753","article-title":"Polycomb repressive complex 1 provides a molecular explanation for repeat copy number dependency in FSHD muscular dystrophy","volume":"26","author":"Casa","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.cell.2013.06.044","article-title":"XCRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes","volume":"154","author":"Gilbert","year":"2013","journal-title":"Cell"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"11837","DOI":"10.1074\/jbc.RA118.002633","article-title":"Protein kinase A activation inhibits DUX4 gene expression in myotubes from patients with facioscapulohumeral muscular dystrophy","volume":"293","author":"Cruz","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1124\/jpet.119.264689","article-title":"p38a Regulates Expression of DUX4 in a Model of Facioscapulohumeral Muscular Dystrophys","volume":"374","author":"Rojas","year":"2020","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1002\/acn3.51063","article-title":"Remote ischemic conditioning combined with intravenous thrombolysis for acute ischemic stroke","volume":"7","author":"He","year":"2020","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"bio033977","DOI":"10.1242\/bio.033977","article-title":"Functional domains of the FSHD-associated DUX4 protein","volume":"7","author":"Mitsuhashi","year":"2018","journal-title":"Biol. Open"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/2044-5040-4-4","article-title":"High-throughput screening identifies inhibitors of DUX4-induced myoblast toxicity","volume":"4","author":"Bosnakovski","year":"2014","journal-title":"Skelet. 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