Fig. 7
Functional relevance of DMRs and DNA methylation in MEKi resistance. A Percent of DMRs overlapping with the indicated feature. B TFBS were significantly enriched in all as well as in reverting DMRs compared to 106 random regions of similar length and CpG count (** significance level < 0.01; * significance level < 0.05). C Percent of DMRs that overlap with an ATAC-seq or ChIP-seq H3K27ac peak found in at least 2 organoids by Roe and co-workers [34]. D, E Enrichment for ATAC-seq (D) or H3K27ac (E) peaks relative to 106 random regions of similar length and CpG count (*** significance level < 0.001; ** significance level < 0.01). F Venn diagram of reverting DMRs’ overlap with TFBS and/or H3K27ac peaks. G Enrichment of TFBS for the indicated transcription factors in the 217 reverting DMRs compared to 1974 non-reverting DMRs. H Enrichment of TFBS motifs from the homer database between the reverting DMRs and random background sequences. I NES of AP1 related gene expression signatures that are significantly (FDR < 0.25) different between parental and resistant cells based on GSEA of RNA-seq data. J Enrichment plot of the AP1_Q6 gene expression signature