{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:40:57Z","timestamp":1791942057311,"version":"4.3.4"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,11,2]],"date-time":"2023-11-02T00:00:00Z","timestamp":1698883200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007540","name":"Jiangsu Agricultural Science and Technology Innovation Fund","doi-asserted-by":"publisher","award":["CX (20) 2011"],"award-info":[{"award-number":["CX (20) 2011"]}],"id":[{"id":"10.13039\/100007540","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["KYQN2022030"],"award-info":[{"award-number":["KYQN2022030"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["KYT2023002"],"award-info":[{"award-number":["KYT2023002"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31972564"],"award-info":[{"award-number":["31972564"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31972571"],"award-info":[{"award-number":["31972571"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Lactate, a glycolytic metabolite mainly produced in muscles, has been suggested to regulate myoblast differentiation, although the underlying mechanism remains elusive. Recently, lactate\u2010mediated histone lactylation is identified as a novel epigenetic modification that promotes gene transcription.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used mouse C2C12 cell line and 2\u2010month\u2010old male mice as in vitro and in vivo models, respectively. These models were treated with lactate to explore the biological function and latent mechanism of lactate\u2010derived histone lactylation on myogenic differentiation by quantitative real\u2010time PCR, western blotting, immunofluorescence staining, chromatin immunoprecipitation, cleavage under targets and tagmentation assay and RNA sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Using immunofluorescence staining and western blotting, we proposed that lactylation might occur in the histones. Inhibition of lactate production or intake both impaired myoblast differentiation, accompanied by diminished lactylation in the histones. Using lactylation site\u2010specific antibodies, we demonstrated that lactate preferentially increased H3K9 lactylation (H3K9la) during myoblast differentiation (CT VS 5, 10, 15, 20, 25\u00a0mM lactate treatment, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.0012, <jats:italic>P\u00a0=<\/jats:italic>\u00a00.0007, and the rest of all <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001). Notably, inhibiting H3K9la using P300 antagonist could block lactate\u2010induced myogenesis. Through combined omics analysis using cleavage under targets and tagmentation assay and RNA sequencing, we further identified <jats:italic>Neu2<\/jats:italic> as a potential target gene of H3K9la. IGV software analysis (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0013) and chromatin immunoprecipitation\u2010qPCR assay (H3K9la %Input, LA group\u00a0=\u00a09.0076, control group\u00a0=\u00a02.7184, IgG\u00a0=\u00a00.3209) confirmed that H3K9la is enriched in the promoter region of <jats:italic>Neu2<\/jats:italic>. Moreover, siRNAs or inhibitors against Neu2 both abrogated myoblast differentiation despite lactate treatment, suggesting that Neu2 is required for lactate\u2010mediated myoblast differentiation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings provide novel understanding of histone lysine lactylation, suggesting its role in myogenesis, and as potential therapeutic targets for muscle diseases.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13363","type":"journal-article","created":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T03:24:15Z","timestamp":1698981855000},"page":"2851-2865","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":88,"title":["Lactate promotes myogenesis via activating H3K9 lactylation\u2010dependent up\u2010regulation of Neu2 expression"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4297-0411","authenticated-orcid":false,"given":"Weilong","family":"Dai","sequence":"first","affiliation":[{"name":"Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology Nanjing Agricultural University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology Nanjing Agricultural University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology Nanjing Agricultural University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology Nanjing Agricultural University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingli","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology Nanjing Agricultural University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honglin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology Nanjing Agricultural University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology Nanjing Agricultural University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20123-1"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.151035"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c140068"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2014.03.004"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-021-00841-9"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19113649"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.05.004"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101454"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/d41586-019-03122-1"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2020.02.026"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.05.092"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2015.1115172"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagrm.2015.01.002"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1678-1"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2019.215830"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cws057"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(03)00709-9"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-07033-6"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2006.05380.x"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2022.153962"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-7380-4_3"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-021-03799-1"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-021-02308-z"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2009.178350"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2012.05.003"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1847-2"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2021.09.009"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2019.12.004"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.00190"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/82_2010_78"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-82820-1"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-020-00391-y"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2021.02.025"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.688910"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109820"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.7.2404-2412.2001"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1846704"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M106501200"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80005-2"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80383-4"}],"container-title":["Journal 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