Fig. 5: Turnover at highly methylated cytosines correlates with genomic activity.
a Scatterplot of kde and kme highlighting CpGs in red that have a high steady state ≥70%). b Rates and methylation levels as a function of location in genic regions. Mean values for CpGs are represented as a function of their position in genes as a percentage (i.e., each genic region represents 100 bins). Upstream and downstream of noted TSS and TTS regions represent 10 kb of flanking DNA. Each row in the heatmap represents a collection of genes binned on transcriptional output in RPKM (five bins total), with the highest expressing bin on top. Each bin represents at least 2k genes. c Heatmap representing signal for eight different chromatin marks across bins of highly methylated cytosines (red points from a). Mean histone signal was calculated by tiling the genome into 1 kb bins and determining enrichment in ChIP signal over input for the respective marks. From left to right, bins are split based on mean methylation turnover within the bin, with the highest turnover bin on the far right. Note the increase in H3K36me3 and active marks, with the concomitant decrease in H3K9me2/3. d Turnover increases with proximity to distal regulatory elements. CpGs were binned on turnover as for c, but their distance to the nearest DHS site was calculated. Boxplot elements are as defined in Fig. 4d.
