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In the present study, by using the Stelic animal model of NASH and NASH\u2010derived liver carcinogenesis, we investigated the role of the folate\u2010dependent 1\u2010carbon metabolism in the pathogenesis of NASH. We demonstrated that advanced NASH and NASH\u2010related liver carcinogenesis are characterized by a significant dysregulation of 1\u2010carbon homeostasis, with diminished expression of key 1\u2010carbon metabolism genes, especially a marked inhibition of the S\u2010adenosylhomocysteine hydrolase (\n                    <jats:italic>Ahcy<\/jats:italic>\n                    ) gene and an increased level of S\u2010adenosyl\u2010L\u2010homocysteine (SAH). The reduction in\n                    <jats:italic>Ahcy<\/jats:italic>\n                    expression was associated with gene\u2010specific cytosine DNA hypermethylation and enrichment of the gene promoter by trimethylated histone H3 lysine 27 and deacetylated histone H4 lysine 16, 2 main transcription\u2010inhibiting markers. These results indicate that epigenetically mediated inhibition of\n                    <jats:italic>Ahcy<\/jats:italic>\n                    expression may be a driving force in causing SAH elevation and subsequent downstream disturbances in transsulfuration and transmethylation pathways during the development and progression of NASH.\u2014Pogribny, I. P., Dreval, K., Kindrat, I., Melnyk, S., Jimenez, L., de Conti, A., Tryndyak, V., Pogribna, M., Ortega, J. F., James, S. J., Rusyn, I., Beland, F. A. Epigenetically mediated inhibition of\n                    <jats:italic>S<\/jats:italic>\n                    \u2010adenosylhomocysteine hydrolase and the associated dysregulation of 1\u2010carbon metabolism in nonalcoholic steatohepatitis and hepatocellular carcinoma. FASEB J. 32,1591\u20101601 (2018).\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.201700866r","type":"journal-article","created":{"date-parts":[[2017,11,10]],"date-time":"2017-11-10T12:10:20Z","timestamp":1510315820000},"page":"1591-1601","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Epigenetically mediated inhibition of S\u2010adenosylhomocysteine hydrolase and the associated dysregulation of 1\u2010carbon metabolism in nonalcoholic steatohepatitis and hepatocellular carcinoma"],"prefix":"10.1096","volume":"32","author":[{"given":"Igor P.","family":"Pogribny","sequence":"first","affiliation":[{"name":"Division of Biochemical Toxicology National Center for Toxicological Research Jefferson Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kostiantyn","family":"Dreval","sequence":"additional","affiliation":[{"name":"Division of Biochemical Toxicology National Center for Toxicological Research Jefferson Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iryna","family":"Kindrat","sequence":"additional","affiliation":[{"name":"Division of Biochemical Toxicology National Center for Toxicological Research Jefferson Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stepan","family":"Melnyk","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Arkansas for Medical Sciences Little Rock Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leandro","family":"Jimenez","sequence":"additional","affiliation":[{"name":"Molecular Oncology Center Hospital Sirio\u2010Libanes S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline","family":"de Conti","sequence":"additional","affiliation":[{"name":"Division of Biochemical Toxicology National Center for Toxicological Research Jefferson Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volodymyr","family":"Tryndyak","sequence":"additional","affiliation":[{"name":"Division of Biochemical Toxicology National Center for Toxicological Research Jefferson Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Pogribna","sequence":"additional","affiliation":[{"name":"Division of Biochemical Toxicology National Center for Toxicological Research Jefferson Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana Festa","family":"Ortega","sequence":"additional","affiliation":[{"name":"Division of Biochemical Toxicology National Center for Toxicological Research Jefferson Arkansas USA"},{"name":"Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences University of S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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