{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:59:37Z","timestamp":1791305977312,"version":"4.3.1"},"reference-count":28,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,12,4]],"date-time":"2014-12-04T00:00:00Z","timestamp":1417651200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000062","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":[[2015,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    To investigate the role of enhancer of zeste homolog (EZH) 1 and EZH2 in liver homeostasis, mice were generated that carried\n                    <jats:italic>Ezh1<\/jats:italic>\n                    <jats:sup>\u2010\/\u2010<\/jats:sup>\n                    and\n                    <jats:italic>\n                      EZH2\n                      <jats:sup>fl\/fl<\/jats:sup>\n                    <\/jats:italic>\n                    alleles and an Alb\u2010\n                    <jats:italic>Cre<\/jats:italic>\n                    transgene. Only the combined loss of EZH1 and EZH2 in mouse hepatocytes caused a depletion of global trimethylation on Lys 27 of histone H3 (H3K27me3) marks and the specific loss of over ~1900 genes at 3 mo of age.\n                    <jats:italic>Ezh1<\/jats:italic>\n                    <jats:sup>\u2010\/\u2010<\/jats:sup>\n                    <jats:italic>\n                      ,Ezh2\n                      <jats:sup>fl\/fl<\/jats:sup>\n                      Alb\u2010Cre\n                    <\/jats:italic>\n                    mice exhibited progressive liver abnormalities manifested by the development of regenerative nodules and concomitant periportal fibrosis, inflammatory infiltration, and activation of A6\u2010positive hepatic progenitor cells at 8 mo of age. In response to chronic treatment with carbon tetrachloride, all experimental mice, but none of the controls (\n                    <jats:italic>n<\/jats:italic>\n                    = 27 each), showed increased hepatic degeneration associated with liver dysfunction and reduced ability to proliferate. After two\u2010thirds partial hepatectomy, mutant mice (\n                    <jats:italic>n<\/jats:italic>\n                    = 5) displayed increased liver injury and a blunted regenerative response. Genomewide analyses at 3 mo of age identified 51 genes that had lost H3K27me3 marks, and their expression was significantly increased. These genes were involved in regulation of cell survival, fibrosis, and proliferation. H3K27me3 levels and liver physiology were unaffected in mice lacking either EZH1 globally or EZH2 specifically in hepatocytes. This work demonstrates a critical redundancy of EZH1 and EZH2 in maintaining hepatic homeostasis and regeneration.\u2014Bae, W. K., Kang, K., Yu, J. H., Yoo, K. H., Factor, V. M., Kaji, K., Matter, M., Thorgeirsson, S., Hennighausen, L. The methyltransferases enhancer of zeste homolog (EZH) 1 and EZH2 control hepatocyte homeostasis and regeneration.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    29, 1653\u20101662 (2015).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.14-261537","type":"journal-article","created":{"date-parts":[[2014,12,5]],"date-time":"2014-12-05T00:00:12Z","timestamp":1417737612000},"page":"1653-1662","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["The methyltransferases enhancer of zeste homolog (EZH) 1 and EZH2 control hepatocyte homeostasis and regeneration"],"prefix":"10.1096","volume":"29","author":[{"given":"Woo Kyun","family":"Bae","sequence":"first","affiliation":[{"name":"Laboratory of Genetics and Physiology National Institute of Diabetes and Digestive and Kidney Diseases Bethesda Maryland USA"},{"name":"Department of Internal Medicine Chonnam National University Medical School Gwangju Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keunsoo","family":"Kang","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Physiology National Institute of Diabetes and Digestive and Kidney Diseases Bethesda Maryland USA"},{"name":"Department of Microbiology Dankook University Cheonan Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Hoon","family":"Yu","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Physiology National Institute of Diabetes and Digestive and Kidney Diseases Bethesda Maryland USA"},{"name":"New Drug Development Center, Daegu\u2010Gyeongbuk Medical Innovation Foundation Daegu Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung Hyun","family":"Yoo","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Physiology National Institute of Diabetes and Digestive and Kidney Diseases Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina M.","family":"Factor","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Carcinogenesis Center for Cancer Research, National Cancer Institute, National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosuke","family":"Kaji","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Carcinogenesis Center for Cancer Research, National Cancer Institute, National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Matter","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Carcinogenesis Center for Cancer Research, National Cancer Institute, National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Snorri","family":"Thorgeirsson","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Carcinogenesis Center for Cancer Research, National Cancer Institute, National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lothar","family":"Helmighausen","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Physiology National Institute of Diabetes and Digestive and Kidney Diseases Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,12,4]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2010.08.002"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genet.38.072902.091907"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09784"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2008.11.004"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.2019811"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2651"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.25679"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1227604"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2012.09.004"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2011.11.019"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni876"},{"key":"e_1_2_7_13_1","first-page":"409","article-title":"Origin and fate of oval cells in dipin-induced hepatocarcinogenesis in the mouse","volume":"145","author":"Factor V. 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