{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:29:47Z","timestamp":1790958587690,"version":"4.1.0"},"reference-count":38,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"9","funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01 AR055685"],"award-info":[{"award-number":["R01 AR055685"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009824","name":"FSH Society","doi-asserted-by":"publisher","award":["FSHS-22017-05"],"award-info":[{"award-number":["FSHS-22017-05"]}],"id":[{"id":"10.13039\/100009824","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2019,9,6]]},"abstract":"<jats:p>DUX4 drives global histone H3 hyperacetylation; and a new P300 inhibitor, iP300w, blocks DUX4-mediated transcription and toxicity.<\/jats:p>","DOI":"10.1126\/sciadv.aaw7781","type":"journal-article","created":{"date-parts":[[2019,9,11]],"date-time":"2019-09-11T23:15:15Z","timestamp":1568243715000},"source":"Crossref","is-referenced-by-count":66,"title":["A novel P300 inhibitor reverses DUX4-mediated global histone H3 hyperacetylation, target gene expression, and cell death"],"prefix":"10.1126","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7198-2019","authenticated-orcid":true,"given":"Darko","family":"Bosnakovski","sequence":"first","affiliation":[{"name":"Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA."},{"name":"Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA."},{"name":"Faculty of Medical Sciences, University Goce Delcev\u2014\u0160tip, \u0160tip 2000, Republic of North Macedonia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7479-2595","authenticated-orcid":true,"given":"Meiricris T.","family":"da Silva","sequence":"additional","affiliation":[{"name":"Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA."},{"name":"Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1218-4906","authenticated-orcid":true,"given":"Sithara T.","family":"Sunny","sequence":"additional","affiliation":[{"name":"Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA."},{"name":"Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4147-1146","authenticated-orcid":true,"given":"Elizabeth T.","family":"Ener","sequence":"additional","affiliation":[{"name":"Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA."},{"name":"Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik A.","family":"Toso","sequence":"additional","affiliation":[{"name":"Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA."},{"name":"Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4323-7353","authenticated-orcid":true,"given":"Ce","family":"Yuan","sequence":"additional","affiliation":[{"name":"Bioinformatics and Computational Biology Program, University of Minnesota, Minneapolis, MN 55455, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4002-2509","authenticated-orcid":true,"given":"Ziyou","family":"Cui","sequence":"additional","affiliation":[{"name":"Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA."},{"name":"Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5650-9277","authenticated-orcid":true,"given":"Michael A.","family":"Walters","sequence":"additional","affiliation":[{"name":"Institute for Therapeutics Discovery and Development, University of Minnesota, Minneapolis, MN 55455, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7955-1451","authenticated-orcid":true,"given":"Ajit","family":"Jadhav","sequence":"additional","affiliation":[{"name":"National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5579-7534","authenticated-orcid":true,"given":"Michael","family":"Kyba","sequence":"additional","affiliation":[{"name":"Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA."},{"name":"Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000797"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/ng1262","article-title":"Hypomethylation of D4Z4 in 4q-linked and non-4q-linked facioscapulohumeral muscular dystrophy","volume":"35","author":"van Overveld P. G. M.","year":"2003","unstructured":"P. G. M. van Overveld, R. J. F. L. Lemmers, L. A. Sandkuijl, L. Enthoven, S. T. Winokur, F. Bakels, G. W. Padberg, G.-J. B. van Ommen, R. R. Frants, S. M. van der Maarel, Hypomethylation of D4Z4 in 4q-linked and non-4q-linked facioscapulohumeral muscular dystrophy. Nat. Genet. 35, 315\u2013317 (2003).","journal-title":"Nat. Genet."},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1093\/hmg\/2.12.2037","article-title":"FSHD associated DNA rearrangements are due to deletions of integral copies of a 3.2 kb tandemly repeated unit","volume":"2","author":"Van Deutekom J. C. T.","year":"1993","unstructured":"J. C. T. Van Deutekom, C. Wljmenga, E. A. E. Van Tlenhoven, A.-M. Gruter, J. E. Hewitt, G. W. Padberg, G.-J. B. van Ommen, M. H. Hofker, R. R. Fronts, FSHD associated DNA rearrangements are due to deletions of integral copies of a 3.2 kb tandemly repeated unit. Hum. Mol. Genet. 2, 2037\u20132042 (1993).","journal-title":"Hum. Mol. Genet."},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2454"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1189044"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(99)00267-X"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3844"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3846"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3858"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2008.201"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv315"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2007.04.002"},{"key":"e_1_3_2_14_2","doi-asserted-by":"crossref","first-page":"3685","DOI":"10.1242\/jcs.205427","article-title":"The DUX4 homeodomains mediate inhibition of myogenesis and are functionally exchangeable with the Pax7 homeodomain","volume":"130","author":"Bosnakovski D.","year":"2017","unstructured":"D. Bosnakovski, E. A. Toso, L. M. Hartweck, A. Magli, H. A. Lee, E. R. Thompson, A. Dandapat, R. C. R. Perlingeiro, M. Kyba, The DUX4 homeodomains mediate inhibition of myogenesis and are functionally exchangeable with the Pax7 homeodomain. J. Cell Sci. 130, 3685\u20133697 (2017).","journal-title":"J. Cell Sci."},{"key":"e_1_3_2_15_2","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 D.","year":"2017","unstructured":"D. Bosnakovski, S. S. K. Chan, O. O. Recht, L. M. Hartweck, C. J. Gustafson, L. L. Athman, D. A. Lowe, M. Kyba, Muscle pathology from stochastic low level DUX4 expression in an FSHD mouse model. Nat. Commun. 8, 550 (2017).","journal-title":"Nat. Commun."},{"key":"e_1_3_2_16_2","doi-asserted-by":"crossref","first-page":"e0192657","DOI":"10.1371\/journal.pone.0192657","article-title":"A cre-inducible DUX4 transgenic mouse model for investigating facioscapulohumeral muscular dystrophy","volume":"13","author":"Jones T.","year":"2018","unstructured":"T. Jones, P. L. Jones, A cre-inducible DUX4 transgenic mouse model for investigating facioscapulohumeral muscular dystrophy. PLOS ONE 13, e0192657 (2018).","journal-title":"PLOS ONE"},{"key":"e_1_3_2_17_2","doi-asserted-by":"crossref","first-page":"123538","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 C. R.","year":"2018","unstructured":"C. R. Giesige, L. M. Wallace, K. N. Heller, J. O. Eidahl, N. Y. Saad, A. M. Fowler, N. K. Pyne, M. Al-Kharsan, A. Rashnonejad, G. A. Chermahini, J. S. Domire, D. Mukweyi, S. E. Garwick-Coppens, S. M. Guckes, K. J. McLaughlin, K. Meyer, L. R. Rodino-Klapac, S. Q. Harper, AAV-mediated follistatin gene therapy improves functional outcomes in the TIC-DUX4 mouse model of FSHD. JCI Insight 3, 123538 (2018).","journal-title":"JCI Insight"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu251"},{"key":"e_1_3_2_19_2","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 J. K.","year":"2018","unstructured":"J. K. Lee, D. Bosnakovski, E. A. Toso, T. Dinh, S. Banerjee, T. E. Bohl, K. Shi, K. Orellana, M. Kyba, H. Aihara, Crystal structure of the double homeodomain of DUX4 in complex with DNA. Cell Rep. 25, 2955\u20132962.e3 (2018).","journal-title":"Cell Rep."},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw141"},{"key":"e_1_3_2_21_2","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1038\/s41467-017-01657-3","article-title":"Assay interference and off-target liabilities of reported histone acetyltransferase inhibitors","volume":"8","author":"Dahlin J. L.","year":"2017","unstructured":"J. L. Dahlin, K. M. Nelson, J. M. Strasser, D. Barsyte-Lovejoy, M. M. Szewczyk, S. Organ, M. Cuellar, G. Singh, J. H. Shrimp, N. Nguyen, J. L. Meier, C. H. Arrowsmith, P. J. Brown, J. B. Baell, M. A. Walters, Assay interference and off-target liabilities of reported histone acetyltransferase inhibitors. Nat. Commun. 8, 1527 (2017).","journal-title":"Nat. Commun."},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2010.03.006"},{"key":"e_1_3_2_23_2","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1021\/acsmedchemlett.5b00385","article-title":"Characterizing the covalent targets of a small molecule inhibitor of the lysine acetyltransferase P300","volume":"7","author":"Shrimp J. H.","year":"2016","unstructured":"J. H. Shrimp, A. W. Sorum, J. M. Garlick, L. Guasch, M. C. Nicklaus, J. L. Meier, Characterizing the covalent targets of a small molecule inhibitor of the lysine acetyltransferase P300. ACS Med. Chem. Lett. 7, 151\u2013155 (2016).","journal-title":"ACS Med. Chem. Lett."},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature24028"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2007.00306.x"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07619"},{"key":"e_1_3_2_27_2","doi-asserted-by":"crossref","first-page":"16957","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 D.","year":"2018","unstructured":"D. Bosnakovski, M. D. Gearhart, E. A. Toso, E. T. Ener, S. H. Choi, M. Kyba, Low level DUX4 expression disrupts myogenesis through deregulation of myogenic gene expression. Sci. Rep. 8, 16957 (2018).","journal-title":"Sci. Rep."},{"key":"e_1_3_2_28_2","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1016\/j.ajpath.2012.07.007","article-title":"Generation of isogenic D4Z4 contracted and noncontracted immortal muscle cell clones from a mosaic patient: A cellular model for FSHD","volume":"181","author":"Krom Y. D.","year":"2012","unstructured":"Y. D. Krom, J. Dumonceaux, K. Mamchaoui, B. den Hamer, V. Mariot, E. Negroni, L. N. Geng, N. Martin, R. Tawil, S. J. Tapscott, B. G. van Engelen, V. Mouly, G. S. Butler-Browne, S. M. van der Maarel, Generation of isogenic D4Z4 contracted and noncontracted immortal muscle cell clones from a mosaic patient: A cellular model for FSHD. Am. J. Pathol. 181, 1387\u20131401 (2012).","journal-title":"Am. J. Pathol."},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2015"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2014"},{"key":"e_1_3_2_31_2","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 J.","year":"2007","unstructured":"J. Clapp, L. M. Mitchell, D. J. Bolland, J. Fantes, A. E. Corcoran, P. J. Scotting, J. A. L. Armour, J. E. Hewitt, Evolutionary conservation of a coding function for D4Z4, the tandem DNA repeat mutated in facioscapulohumeral muscular dystrophy. Am. J. Hum. Genet. 81, 264\u2013279 (2007).","journal-title":"Am. J. Hum. Genet."},{"key":"e_1_3_2_32_2","doi-asserted-by":"crossref","first-page":"e7003","DOI":"10.1371\/journal.pone.0007003","article-title":"Biphasic myopathic phenotype of mouse DUX, an ORF within conserved FSHD-related repeats","volume":"4","author":"Bosnakovski D.","year":"2009","unstructured":"D. Bosnakovski, R. S. Daughters, Z. Xu, J. M. W. Slack, M. Kyba, Biphasic myopathic phenotype of mouse DUX, an ORF within conserved FSHD-related repeats. PLOS ONE 4, e7003 (2009).","journal-title":"PLOS ONE"},{"key":"e_1_3_2_33_2","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 D.","year":"2014","unstructured":"D. Bosnakovski, S. H. Choi, J. M. Strasser, E. A. Toso, M. A. Walters, M. Kyba, High-throughput screening identifies inhibitors of DUX4-induced myoblast toxicity. Skelet. Muscle 4, 4 (2014).","journal-title":"Skelet. Muscle"},{"key":"e_1_3_2_34_2","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 S. H.","year":"2016","unstructured":"S. H. Choi, D. Bosnakovski, J. M. Strasser, E. A. Toso, M. A. Walters, M. Kyba, Transcriptional Inhibitors Identified in a 160,000-Compound Small-Molecule DUX4 Viability Screen. J. Biomol. Screen. 21, 680\u2013688 (2016).","journal-title":"J. Biomol. Screen."},{"key":"e_1_3_2_35_2","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1007\/s13311-018-00675-3","article-title":"Facioscapulohumeral muscular dystrophy: Update on pathogenesis and future treatments","volume":"15","author":"Hamel J.","year":"2018","unstructured":"J. Hamel, R. Tawil, Facioscapulohumeral muscular dystrophy: Update on pathogenesis and future treatments. Neurotherapeutics 15, 863\u2013871 (2018).","journal-title":"Neurotherapeutics"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu170"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3317"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt656"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp616"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.aaw7781","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,23]],"date-time":"2024-07-23T08:15:48Z","timestamp":1721722548000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.aaw7781"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,6]]},"references-count":38,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2019,9,6]]}},"alternative-id":["10.1126\/sciadv.aaw7781"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.aaw7781","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,6]]},"article-number":"eaaw7781"}}