{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:14:48Z","timestamp":1790799288185,"version":"4.1.0"},"reference-count":44,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"18","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2024,5,3]]},"abstract":"<jats:p>The most common form of facioscapulohumeral dystrophy (FSHD1) is caused by a partial loss of the D4Z4 macrosatellite repeat array in the subtelomeric region of chromosome 4. Patients with FSHD1 typically carry 1 to 10 D4Z4 repeats, whereas nonaffected individuals have 11 to 150 repeats. The ~150-kilobyte subtelomeric region of the chromosome 10q exhibits a ~99% sequence identity to the 4q, including the D4Z4 array. Nevertheless, contractions of the chr10 array do not cause FSHD or any known disease, as in most people D4Z4 array on chr10 is flanked by the nonfunctional polyadenylation signal, not permitting the DUX4 expression. Here, we attempted to correct the FSHD genotype by a CRISPR-Cas9\u2013induced exchange of the chr4 and chr10 subtelomeric regions. We demonstrated that the induced t(4;10) translocation can generate recombinant genotypes translated into improved FSHD phenotype. FSHD myoblasts with the t(4;10) exhibited reduced expression of the DUX4 targets, restored PAX7 target expression, reduced sensitivity to oxidative stress, and improved differentiation capacity.<\/jats:p>","DOI":"10.1126\/sciadv.adl1922","type":"journal-article","created":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T17:58:46Z","timestamp":1714586326000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":6,"title":["Exchange of subtelomeric regions between chromosomes 4q and 10q reverts the FSHD genotype and phenotype"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5009-4207","authenticated-orcid":true,"given":"Yinxing","family":"Ma","sequence":"first","affiliation":[{"name":"CNRS UMR9018, Universit\u00e9 Paris-Saclay, Institut Gustave Roussy, Villejuif, France."},{"name":"Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6830-149X","authenticated-orcid":true,"given":"Anna","family":"Schwager (Karpukhina)","sequence":"additional","affiliation":[{"name":"CNRS UMR9018, Universit\u00e9 Paris-Saclay, Institut Gustave Roussy, Villejuif, France."},{"name":"Koltzov Institute of Developmental Biology, Moscow, Russia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Dib","sequence":"additional","affiliation":[{"name":"CNRS UMR9018, Universit\u00e9 Paris-Saclay, Institut Gustave Roussy, Villejuif, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7616-0201","authenticated-orcid":true,"given":"Candice","family":"Gautier","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris Cit\u00e9, Institut Imagine, Inserm U1163, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2574-3874","authenticated-orcid":true,"given":"Olivier","family":"Hermine","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris Cit\u00e9, Institut Imagine, Inserm U1163, Paris, France."},{"name":"Department of Hematology, H\u00f4pital Necker Enfants Malades, AP-HP, Facult\u00e9 de M\u00e9decine Paris Descartes, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9617-5336","authenticated-orcid":true,"given":"Eric","family":"Allemand","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris Cit\u00e9, Institut Imagine, Inserm U1163, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3101-7043","authenticated-orcid":true,"given":"Yegor S.","family":"Vassetzky","sequence":"additional","affiliation":[{"name":"CNRS UMR9018, Universit\u00e9 Paris-Saclay, Institut Gustave Roussy, Villejuif, France."},{"name":"Koltzov Institute of Developmental Biology, Moscow, Russia."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/2044-5040-4-12"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu251"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2011.11.013"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2008.201"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2008.00368.x"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-35150-8"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0026820"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2016.08.007"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-016-1410-2"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2021.102008"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddaa053"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2021.03.008"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1189044"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.2002.6690"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng999"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1086\/521986"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.01.035"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2020-107041"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2018-105949"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1001181"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds284"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2012.07.007"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2012.01647.x"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2022.102251"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-021-04273-8"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw141"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01200-4"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.277871.123"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000708"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1262"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/3.8.1287"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1995.1166"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/mus.880181309"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-01-332064"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2019.05.176"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.25110"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1186\/2044-5040-1-34"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2019.06.022"},{"key":"e_1_3_2_40_2","unstructured":"H. Patel P. Ewels A. Peltzer J. Manning O. Botvinnik G. Sturm M. U. Garcia D. Moreno P. Vemuri nf-core bot M. Binzer-Panchal silviamorins L. Pantano M. Zepper R. Syme A. Talbot G. Kelly F. Hanssen J. A. F. Yates J. Espinosa-Carrasco rfenouil C. Cheshire marchoeppner E. Miller P. Zhou S. Guinchard G. Gabernet C. Mertes D. Straub P. D. Tommaso nf-core\/rnaseq: nf-core\/rnaseq v3.14.0 - Hassium Honey Badger version 3.14.0 (Zenodo 2024); https:\/\/doi.org\/10.5281\/zenodo.10471647."},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4197"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118"},{"key":"e_1_3_2_44_2","doi-asserted-by":"crossref","unstructured":"G. Korotkevich V. Sukhov N. Budin B. Shpak M. N. Artyomov A. Sergushichev Fast gene set enrichment analysis. bioRxiv 060012 [Preprint]. 01 February 2021. https:\/\/doi.org\/10.1101\/060012.","DOI":"10.1101\/060012"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr260"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.adl1922","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T18:00:15Z","timestamp":1714586415000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.adl1922"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,3]]},"references-count":44,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2024,5,3]]}},"alternative-id":["10.1126\/sciadv.adl1922"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.adl1922","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,3]]},"assertion":[{"value":"2023-10-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadl1922"}}