{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:00:30Z","timestamp":1791414030348,"version":"4.3.3"},"reference-count":74,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,5,25]],"date-time":"2024-05-25T00:00:00Z","timestamp":1716595200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,5,25]],"date-time":"2024-05-25T00:00:00Z","timestamp":1716595200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["DP160103559"],"award-info":[{"award-number":["DP160103559"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2024,5,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Alterations to gene transcription and DNA methylation are a feature of many liver diseases including fatty liver disease and liver cancer. However, it is unclear whether the DNA methylation changes are a cause or a consequence of the transcriptional changes. It is even possible that the methylation changes are not required for the transcriptional changes. If DNA methylation is just a minor player in, or a consequence of liver transcriptional change, then future studies in this area should focus on other systems such as histone tail modifications. To interrogate the importance of de novo DNA methylation, we generated mice that are homozygous mutants for both\n                    <jats:italic>Dnmt3a<\/jats:italic>\n                    and\n                    <jats:italic>Dnmt3b<\/jats:italic>\n                    in post\u2010natal liver. These mice are viable and fertile with normal sized livers. Males, but not females, showed increased adipose depots, yet paradoxically, improved glucose tolerance on both control diet and high\u2010fat diets (HFD). Comparison of the transcriptome and methylome with\n                    <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\n                    sequencing and whole\u2010genome bisulfite sequencing in adult hepatocytes revealed that widespread loss of methylation in CpG\u2010rich regions in the mutant did not induce loss of homeostatic transcriptional regulation. Similarly, extensive transcriptional changes induced by HFD did not require de novo DNA methylation. The improved metabolic phenotype of the\n                    <jats:italic>Dnmt3a\/3b<\/jats:italic>\n                    mutant mice may be mediated through the dysregulation of a subset of glucose and fat metabolism genes which increase both glucose uptake and lipid export by the liver. However, further work is needed to confirm this.\n                  <\/jats:p>","DOI":"10.1096\/fj.202301546rr","type":"journal-article","created":{"date-parts":[[2024,5,25]],"date-time":"2024-05-25T11:09:58Z","timestamp":1716635398000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Liver\u2010specific deletion of de novo\n                    <scp>DNA<\/scp>\n                    methyltransferases protects against glucose intolerance in high\u2010fat diet\u2010fed male mice"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2748-6840","authenticated-orcid":false,"given":"S.","family":"Yao","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Biomedical Sciences UNSW Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6031-8219","authenticated-orcid":false,"given":"K.","family":"Prates","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Biomedical Sciences UNSW Sydney  Sydney New South Wales Australia"},{"name":"Department of Biotechnology, Genetics, and Cellular Biology State University of Maring\u00e1  Maring\u00e1 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2282-5049","authenticated-orcid":false,"given":"A.","family":"Freydenzon","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience The University of Queensland  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Assante","sequence":"additional","affiliation":[{"name":"Roger Williams Institute of Hepatology Foundation for Liver Research  London UK"},{"name":"Faculty of Life Sciences and Medicine King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5286-5485","authenticated-orcid":false,"given":"A. F.","family":"McRae","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience The University of Queensland  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2285-5117","authenticated-orcid":false,"given":"M. J.","family":"Morris","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Biomedical Sciences UNSW Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0690-4580","authenticated-orcid":false,"given":"N. A.","family":"Youngson","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Biomedical Sciences UNSW Sydney  Sydney New South Wales Australia"},{"name":"Roger Williams Institute of Hepatology Foundation for Liver Research  London UK"},{"name":"Faculty of Life Sciences and Medicine King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,25]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81656-6"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90611-F"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(84)90274-5"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01124-12"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2719"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1534\/g3.116.034785"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp241"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04456-6"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.259309.115"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.4161\/epi.21539"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0118101"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-016-3932-5"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19803-9"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.2337\/db11-1834"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41397-020-0160-7"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21218138"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.07.047"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2017.02.001"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.691738"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/17474124.2020.1736042"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05550-5"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16354-x"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-015-0769-z"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2010.06.050"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2021.105484"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v27.i23.3182"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.3677"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v25.i25.3136"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.51317"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2018.04.018"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep41093"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28563"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002750"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02633"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M413246200"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.1.305"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1159\/000348677"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-015-9476-8"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty560"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4197"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2010-11-10-r106"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3337"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-019-0109-9"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1754"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2016.00258"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00446.2020"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9040791"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23105847"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.21697"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04234-4"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00060-10"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2019080797"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2020107100"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2014.06.018"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1080\/15592294.2016.1253651"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3305"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.93612"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201445035"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-29993-4"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202206068"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-78151-2"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1002"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.200118"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.085464"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-021-00666-9"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0609140103"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00666.2013"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1992.72.2.507"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.20568"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-10-5526-3_3"},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201387038"},{"key":"e_1_2_11_73_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1233"},{"key":"e_1_2_11_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygeno.2011.05.003"},{"key":"e_1_2_11_75_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg110"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202301546RR","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202301546RR","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T01:18:19Z","timestamp":1761700699000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.202301546RR"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,25]]},"references-count":74,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2024,5,31]]}},"alternative-id":["10.1096\/fj.202301546RR"],"URL":"https:\/\/doi.org\/10.1096\/fj.202301546rr","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,25]]},"assertion":[{"value":"2023-08-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e23690"}}