{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T19:06:23Z","timestamp":1773515183423,"version":"3.50.1"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T00:00:00Z","timestamp":1734307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"JSPS KAKENHI"},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Myotonic dystrophy type 1 (DM1) is a dominantly inherited multi-system disease caused by expanded CTG repeats in the 3\u2032 untranslated region of the dystrophia myotonica protein kinase (DMPK) gene. Similar to other repeat disorders, the expanded trinucleotide repeat is unstable and demonstrates a tendency to increase repeat size with age in affected tissues. DNA mismatch repair system is implicated in somatic instability. It has been demonstrated that DM1 patient-derived induced pluripotent stem cells (DM1-iPSCs) show repeat instability, in which involvement of mismatch repair proteins has been suggested. Here we identified ZNF850 as a novel CTG repeat expansion-related molecule in DM1-iPSCs. ZNF850 was downregulated in a DM1-iPSC clone whose CTG repeat is exceptionally stable. We found that RNAi-mediated ZNF850 downregulation in DM1-iPSCs significantly reduced the repeat expansion and resulting instability. In adult skeletal muscle tissue of DM1 patients, ZNF850 expression levels were positively correlated with the repeat size. Furthermore, we found that ZNF850 protein can bind to the expanded CTG repeat sequence, and is located in proximity to MutS\u03b2 components. These results suggest that ZNF850 might play a role in repeat instability in DM1 by recruiting MutS\u03b2 to the repeat sequence.<\/jats:p>","DOI":"10.1093\/hmg\/ddae186","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T14:27:47Z","timestamp":1734359267000},"page":"327-337","source":"Crossref","is-referenced-by-count":2,"title":["Identification of ZNF850 as a novel CTG repeat expansion-related gene in myotonic dystrophy type 1 patient-derived iPSCs"],"prefix":"10.1093","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2895-3255","authenticated-orcid":false,"given":"Masayoshi","family":"Kamon","sequence":"first","affiliation":[{"name":"Department of Peripheral Nervous System Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry , 4-1-1, Ogawa-Higashi, Kodaira, Tokyo 187-8502 ,","place":["Japan"]},{"name":"Department of Developmental Biology and Functional Genomics, Ehime University School of Medicine , 454 Shitsukawa, Toon, Ehime 791-0295 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuji","family":"Wakatsuki","sequence":"additional","affiliation":[{"name":"Department of Peripheral Nervous System Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry , 4-1-1, Ogawa-Higashi, Kodaira, Tokyo 187-8502 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4714-3044","authenticated-orcid":false,"given":"Masayuki","family":"Nakamori","sequence":"additional","affiliation":[{"name":"Department of Neurology, Osaka University Graduate School of Medicine , 2-2 Yamadaoka, Suita, Osaka 565-0871 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masanori P","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Clinical Neurophysiology, Department of Clinical Laboratory and Biomedical Sciences, Osaka University Graduate School of Medicine , 1-7 Yamadaoka, Suita, Osaka 565-0871 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madoka","family":"Mori-Yoshimura","sequence":"additional","affiliation":[{"name":"Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry , 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8551 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirofumi","family":"Komaki","sequence":"additional","affiliation":[{"name":"Translational Medical Center, National Center of Neurology and Psychiatry , 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8551 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3625-2042","authenticated-orcid":false,"given":"Toshiyuki","family":"Araki","sequence":"additional","affiliation":[{"name":"Department of Peripheral Nervous System Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry , 4-1-1, Ogawa-Higashi, Kodaira, Tokyo 187-8502 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,12,16]]},"reference":[{"key":"2025021107010435500_ref1","first-page":"188","volume-title":"Myotonic dystrophy: disease mechanism, current management and therapeutic development","author":"Araki","year":"2018"},{"key":"2025021107010435500_ref2","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1042\/BST0371281","article-title":"Pathogenic mechanisms of myotonic dystrophy","volume":"37","author":"Lee","year":"2009","journal-title":"Biochem Soc Trans"},{"key":"2025021107010435500_ref3","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1002\/ana.23992","article-title":"Splicing biomarkers of disease severity in myotonic dystrophy","volume":"74","author":"Sobczak","year":"2013","journal-title":"Ann Neurol"},{"key":"2025021107010435500_ref4","doi-asserted-by":"crossref","first-page":"104533","DOI":"10.1016\/j.nbd.2019.104533","article-title":"Molecular genetics of congenital myotonic dystrophy","volume":"132","author":"Lanni","year":"2019","journal-title":"Neurobiol Dis"},{"key":"2025021107010435500_ref5","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1038\/s41580-021-00382-6","article-title":"Molecular mechanisms underlying nucleotide repeat expansion disorders","volume":"22","author":"Malik","year":"2021","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2025021107010435500_ref6","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s12017-019-08572-4","article-title":"Variation in DNA repair system gene as an additional modifier of age at onset in spinocerebellar ataxia type 3\/Machado\u2013Joseph disease","volume":"22","author":"Mergener","year":"2020","journal-title":"NeuroMolecular Med"},{"key":"2025021107010435500_ref7","doi-asserted-by":"crossref","first-page":"e1003280","DOI":"10.1371\/journal.pgen.1003280","article-title":"MSH3 polymorphisms and protein levels affect CAG repeat instability in Huntington\u2019s disease mice","volume":"9","author":"Tom\u00e9","year":"2013","journal-title":"PLoS Genet"},{"key":"2025021107010435500_ref8","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1146\/annurev-biochem-060614-034010","article-title":"DNA triplet repeat expansion and mismatch repair","volume":"84","author":"Iyer","year":"2015","journal-title":"Annu Rev Biochem"},{"key":"2025021107010435500_ref9","doi-asserted-by":"crossref","first-page":"5276","DOI":"10.1093\/hmg\/ddt386","article-title":"Length-dependent CTG.CAG triplet-repeat expansion in myotonic dystrophy patient-derived induced pluripotent stem cells","volume":"22","author":"Du","year":"2013","journal-title":"Hum Mol Genet"},{"key":"2025021107010435500_ref10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep11020","article-title":"Large expansion of CTG\u00b7CAG repeats is exacerbated by MutS\u03b2 in human cells","volume":"5","author":"Nakatani","year":"2015","journal-title":"Sci Rep"},{"key":"2025021107010435500_ref11","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/70598","article-title":"Msh2 deficiency prevents in vivo somatic instability of the CAG repeat in Huntington disease transgenic mice","volume":"23","author":"Manley","year":"1999","journal-title":"Nat Genet"},{"key":"2025021107010435500_ref12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep42522","article-title":"Myotonic dystrophy type 1 patient-derived iPSCs for the investigation of CTG repeat instability","volume":"7","author":"Ueki","year":"2017","journal-title":"Sci Rep"},{"key":"2025021107010435500_ref13","doi-asserted-by":"crossref","first-page":"29861","DOI":"10.1074\/jbc.M112.391961","article-title":"Role of mismatch repair enzymes in GAA\u00b7TTC triplet-repeat expansion in friedreich ataxia induced pluripotent stem cells","volume":"287","author":"Du","year":"2012","journal-title":"J Biol Chem"},{"key":"2025021107010435500_ref14","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1038\/nmeth.1591","article-title":"A more efficient method to generate integration-free human iPS cells","volume":"8","author":"Okita","year":"2011","journal-title":"Nat Methods"},{"key":"2025021107010435500_ref15","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1002\/stem.1293","article-title":"An efficient nonviral method to generate integration-free human-induced pluripotent stem cells from cord blood and peripheral blood cells","volume":"31","author":"Okita","year":"2013","journal-title":"Stem Cells"},{"key":"2025021107010435500_ref16","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/nbt1383","article-title":"Marked differences in differentiation propensity among human embryonic stem cell lines","volume":"26","author":"Osafune","year":"2008","journal-title":"Nat Biotechnol"},{"key":"2025021107010435500_ref17","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.stem.2016.06.019","article-title":"Epigenetic variation between human induced pluripotent stem cell lines is an indicator of differentiation capacity","volume":"19","author":"Nishizawa","year":"2016","journal-title":"Cell Stem Cell"},{"key":"2025021107010435500_ref18","first-page":"417","article-title":"Identification of restriction endonucleases sensitive to 5-cytosine methylation at non-CpG sites, including expanded (CAG)n\/(CTG)n repeats","volume":"6","author":"Castel","year":"2011","journal-title":"Epigenetics"},{"key":"2025021107010435500_ref19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/hmg\/ddq427","article-title":"Expanded CTG repeat demarcates a boundary for abnormal CpG methylation in myotonic dystrophy patient tissues","volume":"20","author":"Castel","year":"2011","journal-title":"Hum Mol Genet"},{"key":"2025021107010435500_ref20","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1074\/mcp.M113.035600","article-title":"Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics","volume":"13","author":"Fagerberg","year":"2014","journal-title":"Mol Cell Proteomics"},{"key":"2025021107010435500_ref21","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1002\/acn3.271","article-title":"Oral administration of erythromycin decreases RNA toxicity in myotonic dystrophy","volume":"3","author":"Nakamori","year":"2016","journal-title":"Ann Clin Transl Neurol"},{"key":"2025021107010435500_ref22","doi-asserted-by":"crossref","first-page":"4134","DOI":"10.1074\/jbc.REV119.007678","article-title":"On the wrong DNA track: molecular mechanisms of repeat-mediated genome instability","volume":"295","author":"Khristich","year":"2020","journal-title":"J Biol Chem"},{"key":"2025021107010435500_ref23","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.jmb.2005.10.059","article-title":"Analysis of interactions between mismatch repair initiation factors and the replication processivity factor PCNA","volume":"355","author":"Lee","year":"2006","journal-title":"J Mol Biol"},{"key":"2025021107010435500_ref24","doi-asserted-by":"crossref","first-page":"2667","DOI":"10.1093\/nar\/gkac075","article-title":"SLX4 dampens MutS\u03b1-dependent mismatch repair","volume":"50","author":"Guervilly","year":"2022","journal-title":"Nucleic Acids Res"},{"key":"2025021107010435500_ref25","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.cell.2007.11.019","article-title":"Induction of pluripotent stem cells from adult human fibroblasts by defined factors","volume":"131","author":"Takahashi","year":"2007","journal-title":"Cell"},{"key":"2025021107010435500_ref26","doi-asserted-by":"crossref","DOI":"10.1371\/annotation\/63972dc9-3a31-43d0-ad52-bc46fd948c03","article-title":"Efficient and reproducible myogenic differentiation from human iPS cells: prospects for Modeling Miyoshi myopathy In vitro","volume":"8","author":"Tanaka","year":"2013","journal-title":"PLoS One"},{"key":"2025021107010435500_ref27","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1093\/hmg\/ddq501","article-title":"Bidirectional transcription stimulates expansion and contraction of expanded (CTG)\u2022(CAG) repeats","volume":"20","author":"Nakamori","year":"2011","journal-title":"Hum Mol Genet"},{"key":"2025021107010435500_ref28","doi-asserted-by":"crossref","first-page":"2222","DOI":"10.1038\/mt.2011.191","article-title":"Stabilization of expanded (CTG).(CAG) repeats by antisense oligonucleotides","volume":"19","author":"Nakamori","year":"2011","journal-title":"Mol Ther"},{"key":"2025021107010435500_ref29","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/0378-1119(91)90434-D","article-title":"Efficient selection for high-expression transfectants with a novel eukaryotic vector","volume":"108","author":"Niwa","year":"1991","journal-title":"Gene"},{"key":"2025021107010435500_ref30","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.molcel.2011.07.039","article-title":"Serine 403 phosphorylation of p62\/SQSTM1 regulates selective autophagic clearance of ubiquitinated proteins","volume":"44","author":"Matsumoto","year":"2011","journal-title":"Mol Cell"},{"key":"2025021107010435500_ref31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep12831","article-title":"Early pathogenesis of Duchenne muscular dystrophy modelled in patient-derived human induced pluripotent stem cells","volume":"5","author":"Shoji","year":"2015","journal-title":"Sci Rep"},{"key":"2025021107010435500_ref32","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.scr.2017.10.023","article-title":"A human iPS cell myogenic differentiation system permitting high-throughput drug screening","volume":"25","author":"Uchimura","year":"2017","journal-title":"Stem Cell Res"},{"key":"2025021107010435500_ref33","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/nbt.3519","article-title":"Near-optimal probabilistic RNA-seq quantification","volume":"34","author":"Bray","year":"2016","journal-title":"Nat Biotechnol"},{"key":"2025021107010435500_ref34","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1038\/nmeth.4324","article-title":"Differential analysis of RNA-seq incorporating quantification uncertainty","volume":"14","author":"Pimentel","year":"2017","journal-title":"Nat Methods"},{"key":"2025021107010435500_ref35","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1093\/nar\/gks1193","article-title":"NCBI GEO: archive for functional genomics data sets - update","volume":"41","author":"Barrett","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"2025021107010435500_ref36","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1212\/01.wnl.0000302174.08951.cf","article-title":"Aberrantly spliced alpha-dystrobrevin alters alpha-syntrophin binding in myotonic dystrophy type 1","volume":"70","author":"Nakamori","year":"2008","journal-title":"Neurology"},{"key":"2025021107010435500_ref37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/braincomms\/fcac154","article-title":"Cell type-specific abnormalities of central nervous system in myotonic dystrophy type 1","volume":"4","author":"Nakamori","year":"2022","journal-title":"Brain Commun"}],"container-title":["Human Molecular Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/hmg\/article-pdf\/34\/4\/327\/61200511\/ddae186.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/hmg\/article-pdf\/34\/4\/327\/61200511\/ddae186.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T07:01:44Z","timestamp":1739257304000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/hmg\/article\/34\/4\/327\/7925495"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,16]]},"references-count":37,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,12,16]]},"published-print":{"date-parts":[[2025,2,8]]}},"URL":"https:\/\/doi.org\/10.1093\/hmg\/ddae186","relation":{},"ISSN":["0964-6906","1460-2083"],"issn-type":[{"value":"0964-6906","type":"print"},{"value":"1460-2083","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,2,15]]},"published":{"date-parts":[[2024,12,16]]}}}