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. 2019 Jul 16;10:3126. doi: 10.1038/s41467-019-11004-3

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© The Author(s) 2019, corrected publication 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 9 — DNA hypermethylation of HNF4α-targets in AH patients. a Heatmap of Log Fold Changes in the expression of main epigenetic modulators in AH patients. Genes are organized by the 12 family of factors described in EpiFactor Database. b, c mRNA abundance in transcripts per million (tpm) from normal livers, AH livers and livers of non-alcohol-related chronic disease of b DNA Methyl-Transferases DNMT1 and c DNMT3A. d–i DNA extracted from 5 Normal and 6 AH livers was bisulfite treated and hybridized in Illumina Infinium MethylationEPIC chip. d heatmap of top 2000 hyper or hypomethylated CpG islands. e DREME and TomTom algorithms (MEME-ChIP suite) were used to search for de novo transcription factor binding sites (tfbs) in hyper and hypomethylated regions and to identify transcription factors known to match these tfbs, respectively. f Differentially methylated regions were gene annotated (nearest-feature) and Ingenuity Pathway Analysis (IPA) was used to predict which transcription factor are predicted to be an upstream regulator genes with DM CpGs. Intensity of the enrichment is presented as Z-Score (p < 0.01). g Selected TF target genes delta-β changes: values are expressed with blue-color gradient if hypermethylated and brown-color if hypomethylated. h RNA sequencing of the same samples used in methylation chip was used to validate potential functional impact of hyper/hypomethylation on gene expression. i IPA analysis of soluble factors upstream the hyper and the hypomethylated region. Intensity of the enrichment is presented as Z-Score. For box-and-whisker plots in b, c, h: perimeters, 25th–75th percentile; midline, median. Gene expression levels are presented in transcripts per million reads (tpm)