Fig. 4: DNA methylation levels at different genomic annotations.

A Average methylation percentage for all WGBS samples (MSS and MSI tumors, normal colon) at chromatin state segmentations obtained from colonic mucosa (E075) tissue in the Roadmap Epigenomics Project. TssA=Active Transcription Start Site (TSS), TssAFlnk=Flanking Active TSS, TxFlnk=Transcr. at gene 5’ and 3’, Tx=Strong transcription, TxWk=Weak transcription, EnhG=Genic enhancers, Enh=enhancers, ZNF/Rpts = ZNF genes & repeats, Het=Heterochromatin, TssBiv=Bivalent/Poised TSS, BivFlnk=Flanking Bivalent TSS/Enh, EnhBiv=Bivalent Enhancer, ReprPC=Repressed PolyComb, ReprPCWk=Weak Repressed PolyComb, Quies=Quiesent/low. Other BRAF mutation=other than V600E (n = 2). B Hierarchical clustering of all WGBS samples (MSS and MSI tumors, normal colon) based on methylation values collected from colonic mucosa BivFlnk areas (Roadmap Epigenomics Project). CIMP-0 = CIMP zero, CIMP-L = CIMP low, CIMP-H = CIMP high. C DNA methylation in MSS BRAF V600E tumors was compared to MSS WT tumors using linear models. Each point represents a result from the linear model from one cell/tissue type and chromatin state in the Roadmap Epigenomics Project data (list of all Roadmap annotations analyzed in Supplementary Table 2). A positive estimate indicates that BRAF mutations were associated with elevated methylation levels at these chromatin states. Results with P-adj. < 0.05 are colored by chromatin state; nonsignificant results are colored with black. D Similar linear models were applied to individual histone modifications and DNAse hypersensitivity regions from the Roadmap Epigenomics Project.