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Previously, we demonstrated that <jats:italic>Col1a1<\/jats:italic> and <jats:italic>Pparg<\/jats:italic> genes are deregulated in CCl<jats:sub>4<\/jats:sub>\u2010induced cirrhosis but their normal expression levels are recovered upon treatment with IFC\u2010305, an adenosine derivative. We observed that adenosine was able to modulate S\u2010adenosylmethionine\u2010dependent <jats:italic>trans<\/jats:italic>\u2010methylation reactions, and recently, we found that IFC\u2010305 modulates <jats:italic>HDAC3<\/jats:italic> expression. Here, we investigated whether epigenetic mechanisms, involving DNA methylation processes and histone acetylation, could explain the re\u2010establishment of gene expression mediated by IFC\u2010305 in cirrhosis. Therefore, Wistar rats were CCl<jats:sub>4<\/jats:sub> treated and a sub\u2010group received IFC\u2010305 to reverse fibrosis. Global changes in DNA methylation, 5\u2010hydroxymethylation, and histone H4 acetylation were observed after treatment with IFC\u2010305. In particular, during cirrhosis, the <jats:italic>Pparg<\/jats:italic> gene promoter is depleted of histone H4 acetylation, whereas IFC\u2010305 administration restores normal histone acetylation levels which correlates with an increase of <jats:italic>Pparg<\/jats:italic> transcript and protein levels. In contrast, the promoter of <jats:italic>Col1a1<\/jats:italic> gene is hypomethylated during cirrhosis but gains DNA methylation upon treatment with IFC\u2010305 which correlates with a reduction of <jats:italic>Col1a1<\/jats:italic> transcript and protein levels. Our results suggest a model in which cirrhosis results in a general loss of permissive chromatin histone marks which triggers the repression of the <jats:italic>Pparg<\/jats:italic> gene and the upregulation of the <jats:italic>Col1a1<\/jats:italic> gene. Treatment with IFC\u2010305 restores epigenetic modifications globally and specifically at the promoters of <jats:italic>Pparg<\/jats:italic> and <jats:italic>Col1a1<\/jats:italic> genes. These results reveal one of the mechanisms of action of IFC\u2010305 and suggest a possible therapeutic function in cirrhosis. J. Cell. Biochem. 119: 401\u2013413, 2018. \u00a9 2017 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcb.26192","type":"journal-article","created":{"date-parts":[[2017,6,7]],"date-time":"2017-06-07T11:48:46Z","timestamp":1496836126000},"page":"401-413","source":"Crossref","is-referenced-by-count":14,"title":["Epigenetic Effects of an Adenosine Derivative in a Wistar Rat Model of Liver Cirrhosis"],"prefix":"10.1002","volume":"119","author":[{"given":"Jes\u00fas Rafael","family":"Rodr\u00edguez\u2010Aguilera","sequence":"first","affiliation":[{"name":"Departamento de Biolog\u00eda Celular y Desarrollo Instituto de Fisiolog\u00eda Celular, UNAM Circuito Exterior s\/n Ciudad Universitaria Coyoac\u00e1n 04510, Cd.Mx. 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