{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T05:42:43Z","timestamp":1793684563922,"version":"4.5.1"},"reference-count":45,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,12,4]],"date-time":"2012-12-04T00:00:00Z","timestamp":1354579200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2013,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Facioscapulohumeral muscular dystrophy (\n                    <jats:styled-content style=\"fixed-case\">FSHD<\/jats:styled-content>\n                    ) is one of the most frequent hereditary muscle disorders. It is linked to contractions of the\n                    <jats:italic>D4Z4<\/jats:italic>\n                    repeat array in 4q35. We have characterized the double homeobox 4 (\n                    <jats:italic>DUX4)<\/jats:italic>\n                    gene in\n                    <jats:italic>D4Z4<\/jats:italic>\n                    and its m\n                    <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\n                    transcribed from the distal\n                    <jats:italic>D4Z4<\/jats:italic>\n                    unit to a polyadenylation signal in the flanking\n                    <jats:italic>pLAM<\/jats:italic>\n                    region. It encodes a transcription factor expressed in\n                    <jats:styled-content style=\"fixed-case\">FSHD<\/jats:styled-content>\n                    but not healthy muscle cells which initiates a gene deregulation cascade causing differentiation defects, muscle atrophy and oxidative stress.\n                    <jats:italic>PITX1<\/jats:italic>\n                    was the first identified\n                    <jats:styled-content style=\"fixed-case\">DUX<\/jats:styled-content>\n                    4 target and encodes a transcription factor involved in muscle atrophy.\n                    <jats:italic>DUX4<\/jats:italic>\n                    was found expressed in only 1\/1000\n                    <jats:styled-content style=\"fixed-case\">FSHD<\/jats:styled-content>\n                    myoblasts. We have now shown it was induced upon differentiation and detected in about 1\/200 myotube nuclei. The\n                    <jats:styled-content style=\"fixed-case\">DUX<\/jats:styled-content>\n                    4 and\n                    <jats:styled-content style=\"fixed-case\">PITX<\/jats:styled-content>\n                    1 proteins presented staining gradients in consecutive myonuclei which suggested a diffusion as known for other muscle nuclear proteins. Both protein half\u2010lifes were regulated by the ubiquitin\u2010proteasome pathway. In addition, we could immunodetect the\n                    <jats:styled-content style=\"fixed-case\">DUX<\/jats:styled-content>\n                    4 protein in\n                    <jats:styled-content style=\"fixed-case\">FSHD<\/jats:styled-content>\n                    muscle extracts. As a model, we propose the\n                    <jats:italic>DUX4<\/jats:italic>\n                    gene is stochastically activated in a small number of\n                    <jats:styled-content style=\"fixed-case\">FSHD<\/jats:styled-content>\n                    myonuclei. The resulting m\n                    <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\n                    s are translated in the cytoplasm around an activated nucleus and the\n                    <jats:styled-content style=\"fixed-case\">DUX<\/jats:styled-content>\n                    4 proteins diffuse to adjacent nuclei where they activate target genes such as\n                    <jats:italic>PITX1<\/jats:italic>\n                    . The\n                    <jats:styled-content style=\"fixed-case\">PITX<\/jats:styled-content>\n                    1 protein can further diffuse to additional myonuclei and expand the transcriptional deregulation cascade initiated by\n                    <jats:styled-content style=\"fixed-case\">DUX<\/jats:styled-content>\n                    4. Together the diffusion and the deregulation cascade would explain how a rare protein could cause the muscle defects observed in\n                    <jats:styled-content style=\"fixed-case\">FSHD<\/jats:styled-content>\n                    .\n                  <\/jats:p>","DOI":"10.1111\/j.1582-4934.2012.01647.x","type":"journal-article","created":{"date-parts":[[2012,12,4]],"date-time":"2012-12-04T12:01:39Z","timestamp":1354622499000},"page":"76-89","source":"Crossref","is-referenced-by-count":163,"title":["<scp>DUX<\/scp>\n                    4 expression in\n                    <scp>FSHD<\/scp>\n                    muscle cells: how could such a rare protein cause a myopathy?"],"prefix":"10.1111","volume":"17","author":[{"given":"Alexandra","family":"Tassin","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Biology Research Institute for Health Sciences and Technology University of Mons Mons Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalila","family":"Laoudj\u2010Chenivesse","sequence":"additional","affiliation":[{"name":"INSERM U1046 Physiologie et M\u00e9decine exp\u00e9rimentale C\u0153ur et Muscle CHU A. de Villeneuve Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Vanderplanck","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology Research Institute for Health Sciences and Technology University of Mons Mons Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marietta","family":"Barro","sequence":"additional","affiliation":[{"name":"INSERM U1046 Physiologie et M\u00e9decine exp\u00e9rimentale C\u0153ur et Muscle CHU A. de Villeneuve Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Charron","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology 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France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9rique","family":"Copp\u00e9e","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology Research Institute for Health Sciences and Technology University of Mons Mons Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Belayew","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology Research Institute for Health Sciences and Technology University of Mons Mons 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