{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:56:28Z","timestamp":1790877388615,"version":"4.1.0"},"reference-count":60,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Skeletal muscle atrophy is a secondary complication in the aetiology of injury and chronic disease. Identifying mechanisms that control muscle mass is necessary to characterise atrophy and develop prevention strategies.\u00a0We aimed to integrate transcriptomic and epigenomic data to identify key regulatory pathways controlled by promoter DNA methylation during muscle unloading. Twenty\u2010one healthy men (20\u201340 years) completed a 4\u2010week standardised exercise programme prior to a 14\u2010day knee brace immobilisation with dietary control. Skeletal muscle mass and strength were assessed before and after immobilisation and biopsies were collected (m. vastus lateralis) before, at 3\u00a0days, and at completion at 14\u00a0days. RNA and DNA were isolated and analysed using Illumina RNA sequencing and DNA methylation 850K EPIC BeadChips. The 14\u2010day immobilisation decreased muscle mass (\u223c9%;\n                    <jats:italic>P\u00a0<\/jats:italic>\n                    &lt;\u00a00.0001) and strength (\u223c16%;\n                    <jats:italic>P\u00a0<\/jats:italic>\n                    &lt;\u00a00.0001). At 3\u00a0days, most biological processes (BPs) were upregulated\/hypomethylated (157 gene sets); upregulated BPs included cell signalling and protein ubiquitination and downregulated BPs included metabolism. After 14\u00a0days, BPs were predominantly downregulated\/hypermethylated, including translation and ribosome biogenesis. Across both time points,\n                    <jats:italic>HDAC4<\/jats:italic>\n                    ,\n                    <jats:italic>GADD45A<\/jats:italic>\n                    and\n                    <jats:italic>CHRNA1<\/jats:italic>\n                    emerged as methylation\u2010regulated candidate mediators of atrophy.\n                    <jats:italic>HDAC4<\/jats:italic>\n                    and\n                    <jats:italic>GADD45A<\/jats:italic>\n                    showed strong correlations primarily at day\u00a03, and\n                    <jats:italic>CHRNA1<\/jats:italic>\n                    remained significant at both time points, extending prior observations in animals to human skeletal muscle. We have characterised changes in gene expression related to hypo\u2010 and hyper\u2010methylation during muscle unloading in humans. These data extend our understanding of the regulatory processes that occur during skeletal muscle atrophy that, at the individual gene level, may be useful in developing strategies for reducing muscle wasting.\n                  <\/jats:p>","DOI":"10.1113\/ep093999","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T20:27:07Z","timestamp":1787603227000},"page":"4763-4780","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi\u2010omics identifies promoter methylation and gene expression changes associated with human skeletal muscle atrophy"],"prefix":"10.1113","volume":"111","author":[{"given":"Jamie\u2010Lee M.","family":"Thompson","sequence":"first","affiliation":[{"name":"Bond Institute of Health and Sport and Faculty of Health Sciences and Medicine Bond University  Gold Coast Queensland Australia"},{"name":"Victor Chang Cardiac Research Institute, Darlinghurst  Sydney Australia"},{"name":"University of New South Wales  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"Doering","sequence":"additional","affiliation":[{"name":"School of Health Medical and Applied Sciences Central Queensland University  Rockhampton Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1189-739X","authenticated-orcid":false,"given":"Boris P.","family":"Budiono","sequence":"additional","affiliation":[{"name":"College of Health and Enablement Flinders University  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen L.","family":"Mackenzie\u2010Shalders","sequence":"additional","affiliation":[{"name":"Bond Institute of Health and Sport and Faculty of Health Sciences and Medicine Bond University  Gold Coast Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin J.","family":"Ashton","sequence":"additional","affiliation":[{"name":"Bond Institute of Health and Sport and Faculty of Health Sciences and Medicine Bond University  Gold Coast Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Dunn","sequence":"additional","affiliation":[{"name":"Bond Institute of Health and Sport and Faculty of Health Sciences and Medicine Bond University  Gold Coast Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6837-1906","authenticated-orcid":false,"given":"Vernon G.","family":"Coffey","sequence":"additional","affiliation":[{"name":"Bond Institute of Health and Sport and Faculty of Health Sciences and Medicine Bond University  Gold Coast Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0006518"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00590.2009"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.100879"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21082756"},{"key":"e_1_2_10_6_1","unstructured":"Blighe K. &Lun A.(2021).PCAtools: PCAtools: Everything principal components analysis.https:\/\/github.com\/kevinblighe\/PCAtools"},{"key":"e_1_2_10_7_1","first-page":"10","article-title":"Recurrent training rejuvenates and enhances transcriptome and methylome responses in young and older human muscle","volume":"5","author":"Blocquiaux S.","year":"2021","journal-title":"Journal of Cachexia, Sarcopenia and Muscle Rapid Communications"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.010389"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00380.2013"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2001.4448"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00115.2006"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2012.04.025"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4467"},{"key":"e_1_2_10_14_1","unstructured":"Conesa A. &Nueda M. 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