Fig. 6: Transcription factor binding shows variable effects on methylation and demethylation activity.

a Rates and TET activity as a function of distal DHS signal. The mouse genome was split into 500 bp bins, and reads tallied for all bins that were completely mappable. Bins were then selected as having a minimum distance of 10 kb from an annotated promoter, and split based on number of DHS reads overlapping these bins. DHS signal increases with increasing bin number, where it is apparent that while kme (left) decreases with increasing accessibility, both kde (middle) and TET activity (right) increase. Boxplot elements are as defined in Fig. 4d. b Rates and TET activity as a function of distance to bound TF motifs. ENCODE ChIP data for 15 TFs was quantified by counting reads surrounding motifs for each TF in a 201 bp window centered on the motif. Each row of the heatmap represents mean rates as a function of distance to the center of the motif for the respective factor. Sites represented here were selected as the top 900 enriched motif occurrences for each factor (see “Methods” for enrichment determination). c Nucleosome positioning, rate of de novo methylation, passive demethylation, and TET activity around bound CTCF sites, color as in b. MNase read counts were shifted by 75 bp to reflect position of the nucleosome dyad. d Model representing the effect of chromatin processes on methylation and demethylation rates. Presence of bound transcription factors can inhibit both processes, while transcription through gene bodies results in increased de novo methylation and passive demethylation. TET proteins in contrast tend to illicit the strongest effect on demethylation rates at accessible regions proximal to bound transcription factors.