Fig. 2
![Fig. 2](http://media.springernature.com/full/springer-static/image/art%3A10.1186%2Fs13148-023-01471-3/MediaObjects/13148_2023_1471_Fig2_HTML.png)
Defining differential DNA methylation among normal kidney and SETD2 wt/mt ccRCC. A Global 5mC of normal kidney (n = 30) and ccRCC regions (n = 138, stratified by SETD2 status). B PCA using all autosomal CpGs (n = 843,393). Each point represents a tissue region. Each region’s shape is representative of the SETD2 status of the tumor it originates from, and the color is representative of the H3K36me3 IHC status of each region. C Unsupervised hierarchical clustering using the 5,000 most variable CpGs across the whole cohort. D Volcano plot of the differential analysis between tumor and normal samples. DMCpGs are represented by red points. E Venn diagram showing the number of DMCpGs (n = 2097) overlapping a selection of three histone marks: H3K27ac, H3K4me1, and H3K4me3. N = 6652 DMCpGs are not represented as they do not overlap with any of the three marks. F Bar plot showing the relative distribution of 2874 hypermethylated and 5875 hypomethylated DMCpGs, normalized to the distribution of CpGs in EPIC array, over four genomic features indicated. Enhancers are defined by loci overlapping with H3K27ac and H3K4me1, but not H3K4me3. CpGs mapped to TSS1500, TSS200, and 5’ UTR, in the EPIC manifest, are considered promoter CpGs. The asterisk indicates a significant distribution difference of the respective feature and the EPIC array total. Y-axis—relative difference (log10) of each feature. G Ontology of enriched pathways derived from 579 and 926 genes linked to the 397 active enhancer and 768 active promoter (defined as positive for H3Kme3 based on normal kidney) DMCpGs, respectively, from panel F, using IPA. The color bar represents the p values as −log10