Fig. 2

Epigenetic zonation along the porto-central axis. a Principal component analysis of the 5000 most variable CpGs (coverage >5 in all samples). Pericentral samples (CV) are coloured in green, the intermediate zone (IZ) in red and the periportal are (PV) in blue. Symbols refer to phenotypic group. b Heatmap of methylation values of the top 1000 DMRs (CpG coverage >10, 500 bp tiles, at least 3 CpGs, FDR < 0.01) between pericentral and periportal that were also covered in the intermediate zone (n = 19). Average CpG methylation differences between CV and PP range between 12.4% and 49.2%. Blue corresponds to low and red to high average methylation values. The annotation legend displays lean controls (NC) in light blue, healthy obese (HO) in dark blue, steatosis (STEA) in red and early NASH (EARLY) in orange. c Genomic annotation of all DMRs (upper pie plot) and of DEG-associated DMRs (lower pie plot). d Visualization of gene expression (purple) and DNA methylation (dark red) z-scores of DEG-associated DMRs and corresponding genes at pericentral (green), intermediate (red) and periportal zone (blue). In the Heatmap yellow corresponds to low z-scores (reduced expression or DNA methylation) and navy to high z-scores (increased expression or DNA methylation)