Fig. 5
Whole genome bisulfite sequencing revealed DMRs mainly hypermethylated in MEKi resistant cells. A Mean gene body methylation levels in parental, resistant, P5 and P12 cell states of cell lines #3 and #9. TSS indicates the transcription start site and TES the transcription end site. B Mean methylation levels of all DMRs and their flanking regions (± 2 kb) in the four indicated cell states of two different cell lines (#3, #9). S indicates the DMR start and E its end. C Circos plot indicates the chromosomal location of 2191 DMRs between two parental and resistant cell lines (circle A). A scoring function was developed to define 217 reverting DMRs whose methylation pattern in P12 resembles that of parental cells (circle B). Circle C displays 15 DMRs that were validated by targeted deep bisulfite sequencing. D Proportion of DMRs hypo- or hypermethylated in resistant cells. E Degree of mouse-human DMR-sequence conservation according to the UCSC liftover tool. F, G Relative location of DMRs on bp level in relation to CpG islands (F) or genes (G) both compared to the mm10 reference genome (p < 0.001; chi-square test)