{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T16:40:56Z","timestamp":1786466456251,"version":"build-2736575974"},"reference-count":93,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T00:00:00Z","timestamp":1748390400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FSHD Canada Foundation","award":["20220204-FSHD"],"award-info":[{"award-number":["20220204-FSHD"]}]},{"name":"FSHD Canada Foundation","award":["FSHD-Fall2020-4060516418"],"award-info":[{"award-number":["FSHD-Fall2020-4060516418"]}]},{"name":"FSHD Canada Foundation","award":["1R21AR080887"],"award-info":[{"award-number":["1R21AR080887"]}]},{"name":"FSHD Canada Foundation","award":["1R01AR081449"],"award-info":[{"award-number":["1R01AR081449"]}]},{"name":"NIH\/NIAMS","award":["20220204-FSHD"],"award-info":[{"award-number":["20220204-FSHD"]}]},{"name":"NIH\/NIAMS","award":["FSHD-Fall2020-4060516418"],"award-info":[{"award-number":["FSHD-Fall2020-4060516418"]}]},{"name":"NIH\/NIAMS","award":["1R21AR080887"],"award-info":[{"award-number":["1R21AR080887"]}]},{"name":"NIH\/NIAMS","award":["1R01AR081449"],"award-info":[{"award-number":["1R01AR081449"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Facioscapulohumeral muscular dystrophy (FSHD) is caused by the aberrant expression of the double homeobox 4 (DUX4) gene. In this study, an analysis of human FSHD muscle biopsies revealed differential expressions of six m6A regulators, including writers, readers and eraser proteins. In immortalized human FSHD myoblasts, we found higher levels of mRNA and protein expression of a major m6A regulator, methyltransferase-like protein 3 (METTL3), in comparison with myoblasts from unaffected siblings (UASbs). Quantification of the overall RNA m6A levels in the FSHD myoblasts revealed significant elevation compared with their UASb, which was reversed to UASb levels following treatment with an antisense oligonucleotide targeting the DUX4 mRNA. Using Oxford Nanopore direct-RNA sequencing, we mapped m6A across the transcriptome and identified genes harboring differential methylated m6A sites, including several involved in iron homeostasis. Western blot protein quantification showed that FSHD myoblasts had higher levels of ferritin-heavy chain-207 isoform and mitoferrin-1. In addition, our data showed elevation in mitochondrial ferrous iron in FSHD myoblasts. Our findings suggest that m6A RNA modifications play a pivotal role in FSHD pathophysiology and may serve as biomarker for this disease.<\/jats:p>","DOI":"10.3390\/ijms26115170","type":"journal-article","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T06:30:26Z","timestamp":1748413826000},"page":"5170","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Increased METTL3 Expression and m6A Methylation in Myoblasts of Facioscapulohumeral Muscular Dystrophy"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7804-5303","authenticated-orcid":false,"given":"Nikolaos","family":"Settas","sequence":"first","affiliation":[{"name":"Center for Genetic Medicine Research, Children\u2019s National Research and Innovation Campus, Washington, DC 20012, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2134-418X","authenticated-orcid":false,"given":"Adam J","family":"Bittel","sequence":"additional","affiliation":[{"name":"Center for Genetic Medicine Research, Children\u2019s National Research and Innovation Campus, Washington, DC 20012, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5813-1893","authenticated-orcid":false,"given":"Yi-Wen","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Genetic Medicine Research, Children\u2019s National Research and Innovation Campus, Washington, DC 20012, USA"},{"name":"Department of Genomics and Precision Medicine, School of Medicine and Health Science, The George Washington University, Washington, DC 20037, USA"},{"name":"Department of Pediatrics, School of Medicine and Health Science, The George Washington University, Washington, DC 20037, USA"},{"name":"Department of Biochemistry and Molecular Medicine, School of Medicine and Health Science, The George Washington University, Washington, DC 20037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/S0960-8966(01)00201-2","article-title":"Genetic characterization of a large, historically significant Utah kindred with facioscapulohumeral dystrophy","volume":"11","author":"Flanigan","year":"2001","journal-title":"Neuromuscul. Disord."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1212\/WNL.0000000000000797","article-title":"Population-based incidence and prevalence of facioscapulohumeral dystrophy","volume":"83","author":"Deenen","year":"2014","journal-title":"Neurology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/0140-6736(90)92148-B","article-title":"Location of facioscapulohumeral muscular dystrophy gene on chromosome 4","volume":"336","author":"Wijmenga","year":"1990","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/0888-7543(91)90348-I","article-title":"Mapping of facioscapulohumeral muscular dystrophy gene to chromosome 4q35-qter by multipoint linkage analysis and in situ hybridization","volume":"9","author":"Wijmenga","year":"1991","journal-title":"Genomics"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/ng0992-26","article-title":"Chromosome 4q DNA rearrangements associated with facioscapulohumeral muscular dystrophy","volume":"2","author":"Wijmenga","year":"1992","journal-title":"Nat. Genet."},{"key":"ref_6","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":"Wijmenga","year":"1993","journal-title":"Hum. Mol. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1997","DOI":"10.1093\/hmg\/5.12.1997","article-title":"Evidence for subtelomeric exchange of 3.3 kb tandemly repeated units between chromosomes 4q35 and 10q26: Implications for genetic counselling and etiology of FSHD1","volume":"5","author":"Bakker","year":"1996","journal-title":"Hum. Mol. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1093\/hmg\/3.8.1287","article-title":"Analysis of the tandem repeat locus D4Z4 associated with facioscapulohumeral muscular dystrophy","volume":"3","author":"Hewitt","year":"1994","journal-title":"Hum. Mol. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0378-1119(99)00267-X","article-title":"Nucleotide sequence of the partially deleted D4Z4 locus in a patient with FSHD identifies a putative gene within each 3.3 kb element","volume":"236","author":"Beckers","year":"1999","journal-title":"Gene"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1006\/geno.2002.6690","article-title":"Genomic analysis of human chromosome 10q and 4q telomeres suggests a common origin","volume":"79","author":"Dickson","year":"2002","journal-title":"Genomics"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1086\/426035","article-title":"Contractions of D4Z4 on 4qB subtelomeres do not cause facioscapulohumeral muscular dystrophy","volume":"75","author":"Lemmers","year":"2004","journal-title":"Am. J. Hum. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/ng999","article-title":"Facioscapulohumeral muscular dystrophy is uniquely associated with one of the two variants of the 4q subtelomere","volume":"32","author":"Lemmers","year":"2002","journal-title":"Nat. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"18157","DOI":"10.1073\/pnas.0708659104","article-title":"DUX4, a candidate gene of facioscapulohumeral muscular dystrophy, encodes a transcriptional activator of PITX1","volume":"104","author":"Dixit","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2414","DOI":"10.1093\/hmg\/ddp180","article-title":"RNA transcripts, miRNA-sized fragments and proteins produced from D4Z4 units: New candidates for the pathophysiology of facioscapulohumeral dystrophy","volume":"18","author":"Snider","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"ref_15","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_16","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1038\/ng.2454","article-title":"Digenic inheritance of an SMCHD1 mutation and an FSHD-permissive D4Z4 allele causes facioscapulohumeral muscular dystrophy type 2","volume":"44","author":"Lemmers","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_17","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_18","doi-asserted-by":"crossref","first-page":"e31023","DOI":"10.7554\/eLife.31023","article-title":"NuRD and CAF-1-mediated silencing of the D4Z4 array is modulated by DUX4-induced MBD3L proteins","volume":"7","author":"Campbell","year":"2018","journal-title":"eLife"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s13072-018-0215-z","article-title":"Sporadic DUX4 expression in FSHD myocytes is associated with incomplete repression by the PRC2 complex and gain of H3K9 acetylation on the contracted D4Z4 allele","volume":"11","author":"Haynes","year":"2018","journal-title":"Epigenetics Chromatin"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Huichalaf, C., Micheloni, S., Ferri, G., Caccia, R., and Gabellini, D. (2014). DNA methylation analysis of the macrosatellite repeat associated with FSHD muscular dystrophy at single nucleotide level. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0115278"},{"key":"ref_21","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":"Lemmers","year":"2003","journal-title":"Nat. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1136\/jmedgenet-2015-103436","article-title":"Allele-specific DNA hypomethylation characterises FSHD1 and FSHD2","volume":"53","author":"Calandra","year":"2016","journal-title":"J. Med. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1111\/cge.14533","article-title":"Best practice guidelines on genetic diagnostics of facioscapulohumeral muscular dystrophy: Update of the 2012 guidelines","volume":"106","author":"Giardina","year":"2024","journal-title":"Clin. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1186\/s13148-024-01747-2","article-title":"Integrating D4Z4 methylation analysis into clinical practice: Improvement of FSHD molecular diagnosis through distinct thresholds for 4qA\/4qA and 4qA\/4qB patients","volume":"16","author":"Strafella","year":"2024","journal-title":"Clin. Epigenetics"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1016\/j.ajhg.2016.03.013","article-title":"Mutations in DNMT3B Modify Epigenetic Repression of the D4Z4 Repeat and the Penetrance of Facioscapulohumeral Dystrophy","volume":"98","author":"Lemmers","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e2441","DOI":"10.1212\/WNL.0000000000009617","article-title":"Homozygous nonsense variant in LRIF1 associated with facioscapulohumeral muscular dystrophy","volume":"94","author":"Hamanaka","year":"2020","journal-title":"Neurology"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Strafella, C., Caputo, V., Bortolani, S., Torchia, E., Megalizzi, D., Trastulli, G., Monforte, M., Colantoni, L., Caltagirone, C., and Ricci, E. (2023). Whole exome sequencing highlights rare variants in CTCF, DNMT1, DNMT3A, EZH2 and SUV39H1 as associated with FSHD. Front. Genet., 14.","DOI":"10.3389\/fgene.2023.1235589"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1515\/bchm2.1982.363.1.33","article-title":"RNA synthesis and processing reactions in a subcellular system from mouse L cells","volume":"363","year":"1982","journal-title":"Hoppe Seylers Z. Physiol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3971","DOI":"10.1073\/pnas.71.10.3971","article-title":"Identification of methylated nucleosides in messenger RNA from Novikoff hepatoma cells","volume":"71","author":"Desrosiers","year":"1974","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","first-page":"1233","article-title":"Purification and cDNA cloning of the AdoMet-binding subunit of the human mRNA (N6-adenosine)-methyltransferase","volume":"3","author":"Bokar","year":"1997","journal-title":"Rna"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/0022-2836(78)90183-3","article-title":"The absolute frequency of labeled N-6-methyladenosine in HeLa cell messenger RNA decreases with label time","volume":"124","author":"Sommer","year":"1978","journal-title":"J. Mol. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1016\/j.cell.2015.05.014","article-title":"N6-methyladenosine Modulates Messenger RNA Translation Efficiency","volume":"161","author":"Wang","year":"2015","journal-title":"Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1016\/j.cell.2015.10.012","article-title":"5\u2032 UTR m6A Promotes Cap-Independent Translation","volume":"163","author":"Meyer","year":"2015","journal-title":"Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.molcel.2016.03.021","article-title":"The m6A Methyltransferase METTL3 Promotes Translation in Human Cancer Cells","volume":"62","author":"Lin","year":"2016","journal-title":"Mol. Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1038\/s41586-018-0538-8","article-title":"mRNA circularization by METTL3-eIF3h enhances translation and promotes oncogenesis","volume":"561","author":"Choe","year":"2018","journal-title":"Nature"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.molcel.2012.10.015","article-title":"ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility","volume":"49","author":"Zheng","year":"2013","journal-title":"Mol. Cell"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1146\/annurev-cellbio-100616-060758","article-title":"Rethinking m6A Readers, Writers, and Erasers","volume":"33","author":"Meyer","year":"2017","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.molcel.2016.01.012","article-title":"Nuclear m6A Reader YTHDC1 Regulates mRNA Splicing","volume":"61","author":"Xiao","year":"2016","journal-title":"Mol. Cell"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e31311","DOI":"10.7554\/eLife.31311","article-title":"YTHDC1 mediates nuclear export of N6-methyladenosine methylated mRNAs","volume":"6","author":"Roundtree","year":"2017","journal-title":"eLife"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1038\/cr.2017.99","article-title":"Ythdc2 is an N6-methyladenosine binding protein that regulates mammalian spermatogenesis","volume":"27","author":"Hsu","year":"2017","journal-title":"Cell Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/s41556-018-0045-z","article-title":"Recognition of RNA N6-methyladenosine by IGF2BP proteins enhances mRNA stability and translation","volume":"20","author":"Huang","year":"2018","journal-title":"Nat. Cell Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1038\/nsmb.3462","article-title":"N6-methyladenosine (m6A) recruits and repels proteins to regulate mRNA homeostasis","volume":"24","author":"Edupuganti","year":"2017","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_43","first-page":"3936","article-title":"Fragile X mental retardation protein modulates the stability of its m6A-marked messenger RNA targets","volume":"27","author":"Zhang","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1016\/j.molcel.2018.05.001","article-title":"Sequence, Structure, and Context Preferences of Human RNA Binding Proteins","volume":"70","author":"Dominguez","year":"2018","journal-title":"Mol. Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.cell.2015.12.038","article-title":"ATPase-Modulated Stress Granules Contain a Diverse Proteome and Substructure","volume":"164","author":"Jain","year":"2016","journal-title":"Cell"},{"key":"ref_46","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_47","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_48","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_49","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1093\/hmg\/ddab352","article-title":"Canine DUXC: Implications for DUX4 retrotransposition and preclinical models of FSHD","volume":"31","author":"Wong","year":"2022","journal-title":"Hum. Mol. Genet."},{"key":"ref_50","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_51","doi-asserted-by":"crossref","first-page":"e41740","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_52","doi-asserted-by":"crossref","first-page":"8304","DOI":"10.3390\/molecules20058304","article-title":"Culture Conditions Affect Expression of DUX4 in FSHD Myoblasts","volume":"20","author":"Pandey","year":"2015","journal-title":"Molecules"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4767","DOI":"10.1074\/jbc.M806235200","article-title":"Mitochondrial DNA damage in iron overload","volume":"284","author":"Gao","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Fuhrmann, D.C., Mondorf, A., Beifu\u00df, J., Jung, M., and Br\u00fcne, B. (2020). Hypoxia inhibits ferritinophagy, increases mitochondrial ferritin, and protects from ferroptosis. Redox Biol., 36.","DOI":"10.1016\/j.redox.2020.101670"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Kotla, N.K., Dutta, P., Parimi, S., and Das, N.K. (2022). The Role of Ferritin in Health and Disease: Recent Advances and Understandings. Metabolites, 12.","DOI":"10.3390\/metabo12070609"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"112642","DOI":"10.1016\/j.celrep.2023.112642","article-title":"Compromised nonsense-mediated RNA decay results in truncated RNA-binding protein production upon DUX4 expression","volume":"42","author":"Campbell","year":"2023","journal-title":"Cell Rep."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1016\/j.cell.2015.08.011","article-title":"HNRNPA2B1 Is a Mediator of m6A-Dependent Nuclear RNA Processing Events","volume":"162","author":"Goodarzi","year":"2015","journal-title":"Cell"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3056","DOI":"10.1128\/MCB.01339-06","article-title":"Rbm15 modulates Notch-induced transcriptional activation and affects myeloid differentiation","volume":"27","author":"Ma","year":"2007","journal-title":"Mol. Cell Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/s41392-020-00450-x","article-title":"The role of m6A modification in the biological functions and diseases","volume":"6","author":"Jiang","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"W45","DOI":"10.1093\/nar\/gkae358","article-title":"ChIP-Atlas 3.0: A data-mining suite to explore chromosome architecture together with large-scale regulome data","volume":"52","author":"Zou","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/s41420-020-00328-5","article-title":"A defined N6-methyladenosine (m6A) profile conferred by METTL3 regulates muscle stem cell\/myoblast state transitions","volume":"6","author":"Gheller","year":"2020","journal-title":"Cell Death Discov."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1134\/S002689331903004X","article-title":"Regulation of m6A RNA Methylation and Its Effect on Myogenic Differentiation in Murine Myoblasts","volume":"53","author":"Chen","year":"2019","journal-title":"Mol. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/s41467-021-27848-7","article-title":"The m6A methyltransferase METTL3 regulates muscle maintenance and growth in mice","volume":"13","author":"Petrosino","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Wang, H., Zhao, X., and Lu, Z. (2021). m6A RNA Methylation Regulators Act as Potential Prognostic Biomarkers in Lung Adenocarcinoma. Front. Genet., 12.","DOI":"10.3389\/fgene.2021.622233"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1038\/nchembio.687","article-title":"N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO","volume":"7","author":"Jia","year":"2011","journal-title":"Nat. Chem. Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"dmm049516","DOI":"10.1242\/dmm.049516","article-title":"DUX4 expression activates JNK and p38 MAP kinases in myoblasts","volume":"15","author":"Brennan","year":"2022","journal-title":"Dis. Model. Mech."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"108632","DOI":"10.1016\/j.isci.2023.108632","article-title":"Voluntary wheel running improves molecular and functional deficits in a murine model of facioscapulohumeral muscular dystrophy","volume":"27","author":"Bittel","year":"2024","journal-title":"iScience"},{"key":"ref_68","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_69","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1038\/s43587-024-00724-x","article-title":"METTL3 governs thymocyte development and thymic involution by regulating ferroptosis","volume":"4","author":"Jing","year":"2024","journal-title":"Nat. Aging"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1007\/s10565-021-09660-7","article-title":"METTL14 promotes doxorubicin-induced cardiomyocyte ferroptosis by regulating the KCNQ1OT1-miR-7-5p-TFRC axis","volume":"39","author":"Zhuang","year":"2023","journal-title":"Cell Biol. Toxicol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"111495","DOI":"10.1016\/j.intimp.2024.111495","article-title":"METTL14 depletion ameliorates ferroptosis in severe acute pancreatitis by increasing the N6-methyladenosine modification of ACSL4 and STA1","volume":"128","author":"Chen","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_72","first-page":"164","article-title":"Review on iron and its importance for human health","volume":"19","author":"Abbaspour","year":"2014","journal-title":"J. Res. Med. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1159\/000362888","article-title":"Physiology of iron metabolism","volume":"41","author":"Waeber","year":"2014","journal-title":"Transfus. Med. Hemother"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1559S","DOI":"10.3945\/ajcn.117.155804","article-title":"Current understanding of iron homeostasis","volume":"106","author":"Anderson","year":"2017","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.3324\/haematol.2012.063974","article-title":"Metalloreductase Steap3 coordinates the regulation of iron homeostasis and inflammatory responses","volume":"97","author":"Zhang","year":"2012","journal-title":"Haematologica"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"6660","DOI":"10.1182\/blood-2011-01-329011","article-title":"A novel type of congenital hypochromic anemia associated with a nonsense mutation in the STEAP3\/TSAP6 gene","volume":"118","author":"Grandchamp","year":"2011","journal-title":"Blood"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Srivastava, A.K., Reutovich, A.A., Hunter, N.J., Arosio, P., and Bou-Abdallah, F. (2023). Ferritin microheterogeneity, subunit composition, functional, and physiological implications. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-46880-9"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1080\/13813450701318583","article-title":"Ferritin and ferritin isoforms I: Structure-function relationships, synthesis, degradation and secretion","volume":"113","author":"Koorts","year":"2007","journal-title":"Arch. Physiol. Biochem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/nrm2838","article-title":"The mechanism of eukaryotic translation initiation and principles of its regulation","volume":"11","author":"Jackson","year":"2010","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1038\/nature15377","article-title":"Dynamic m6A mRNA methylation directs translational control of heat shock response","volume":"526","author":"Zhou","year":"2015","journal-title":"Nature"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Heher, P., Ganassi, M., Weidinger, A., Engquist, E.N., Pruller, J., Nguyen, T.H., Tassin, A., Decl\u00e8ves, A.E., Mamchaoui, K., and Banerji, C.R.S. (2022). Interplay between mitochondrial reactive oxygen species, oxidative stress and hypoxic adaptation in facioscapulohumeral muscular dystrophy: Metabolic stress as potential therapeutic target. Redox Biol., 51.","DOI":"10.1016\/j.redox.2022.102251"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1128\/MCB.01685-08","article-title":"Regulation of mitochondrial iron import through differential turnover of mitoferrin 1 and mitoferrin 2","volume":"29","author":"Paradkar","year":"2009","journal-title":"Mol. Cell Biol."},{"key":"ref_83","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_84","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/ejhg.2011.213","article-title":"A unique library of myogenic cells from facioscapulohumeral muscular dystrophy subjects and unaffected relatives: Family, disease and cell function","volume":"20","author":"Homma","year":"2012","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/2044-5040-1-12","article-title":"Establishment of clonal myogenic cell lines from severely affected dystrophic muscles\u2014CDK4 maintains the myogenic population","volume":"1","author":"Stadler","year":"2011","journal-title":"Skelet. Muscle"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1016\/j.ymthe.2020.10.010","article-title":"DUX4 Transcript Knockdown with Antisense 2\u2032-O-Methoxyethyl Gapmers for the Treatment of Facioscapulohumeral Muscular Dystrophy","volume":"29","author":"Lim","year":"2021","journal-title":"Mol. Ther."},{"key":"ref_87","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., Rowel, Q.L.K., and Jaiswal, J.K. (2020). Membrane Repair Deficit in Facioscapulohumeral Muscular Dystrophy. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21155575"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/s41587-020-0439-x","article-title":"The nf-core framework for community-curated bioinformatics pipelines","volume":"38","author":"Ewels","year":"2020","journal-title":"Nat. Biotechnol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"gkaf018","DOI":"10.1093\/nar\/gkaf018","article-title":"edgeR v4: Powerful differential analysis of sequencing data with expanded functionality and improved support for small counts and larger datasets","volume":"53","author":"Chen","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"4288","DOI":"10.1093\/nar\/gks042","article-title":"Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation","volume":"40","author":"McCarthy","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Stat. Society. Ser. B (Methodol.)"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e77014","DOI":"10.7554\/eLife.77014","article-title":"Mettl3-mediated m6A modification of Fgf16 restricts cardiomyocyte proliferation during heart regeneration","volume":"11","author":"Jiang","year":"2022","journal-title":"eLife"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: An open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/11\/5170\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:42:04Z","timestamp":1760031724000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/11\/5170"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,28]]},"references-count":93,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["ijms26115170"],"URL":"https:\/\/doi.org\/10.3390\/ijms26115170","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,28]]}}}