Fig. 4: Rate combinations are characteristic of particular genomic contexts.

a Scatterplot of k_de and k_me for all cytosines. Dashed lines represent different steady-state methylation levels, which are noted on the right upper borders. b Scatterplots as in a, but with CpGs colored according to overlap with previous genome annotations^52,54. Red points represent CpGs of interest for the particular genomic annotation. For example, in the first panel all CpGs overlapping with promoter regions are shown in red, while all CpGs outside of promoters are shown in gray. The number of CpGs overlapping with each state are noted above the respective panel. A graphical depiction of the genomic annotations for the five different contexts is shown below the scatterplots. c Scatterplot of methylation levels measured in wild-type (x-axis) and TTKO cells (y-axis). Inset: change in k_de as a function of TET activity. Values on the x-axis represent log2(k_de^WT) − log2(k_de^TTKO). The vertical blue line represents CpGs where TET activity has no effect on k_de, while the red vertical line represents a three-fold increase in the demethylation rate as a function of TET activity. Note the almost unimodal shift in steady-state methylation levels underscoring the role of TET proteins as demethylases. d TET mediated changes in k_de as a function of genomic context. TET activity is as defined above in c. Annotated regions are sorted based on mean change in k_de. The box represents the middle 50% of the data, the line inside the box is the median, and whiskers are defined by the most extreme values lying within 1.5 times the interquartile range.