Fig. 2

Schematic overview on genes displaying significant NAFLD dependent methylation changes in the TSS1500 interval and associated transcriptional changes. Genes involved in bile acid homeostasis are shown in the upper panel and genes involved in drug metabolism and disposition are shown in the lower panel. Color codes in the left panels indicate the strength of methylation changes in both gene clusters: category 1 (strong changes, dark yellow) defined as ≥ 50 % of CpG islands changed in genes with ≥7 CpG sites within the TSS1500 interval; category 2 (medium strong, yellow) defined as ≥50 % of CpG islands changed in genes with 3 to 6 CpG sites within the TSS1500 interval or 30–50 % of CpG islands changed in genes with ≥ 7 CpG sites); category 3 (small changes, light yellow) defined as < 3 CpG sites within the TSS1500 interval or ≥ 3 CpG islands within the TSS1500 interval and < 30 % of CpG islands changed in methylation. Color codes in the right panels indicate the direction of methylation change in dependency of fibrosis (red, hypermethylation, green, hypomethylation) and the direction of association between methylation and transcription (dark red and dark green, inverse association; light read and light green, parallel association). If no association between methylation and transcription was detected field were left white. The majority of methylation-transcription associations were inverse. Positive associations and correlations were observed for ABCC3, and UGT2B11 (cluster 1), for CYP2B6 (cluster 2) and for NR2B1 (both clusters). SLCO2B1 showed in the majority of cases fibrosis dependent hypermethylated CpG sites (6 of 9 nine sites, one hypomethylated site) and was therefore assigned to the hypermethylated targets