Fig. 8

Methylation gain is concentrated at poised promoters. a UGT1A locus showing siRNA treatment data (top), shRNA lines (middle) and chromatin states (bottom); grey, heterochromatin/low signal; green, transcriptionally active (for full key see previous fig). b Median β levels for probes gaining and losing in shRNA lines (bottom) and median changes in methylation (∆β) versus WT for different chromatin states. c Boxplots of methylation values for probes falling within weak and poised promoter chromatin regions in WT or shRNA lines (averaged). d Transcription at the UGT1A3 and UGT1A6 genes decreases (relative to WT, set to 1) in all three shRNA lines as methylation (β value) increases, as indicated by HT12 and 450K arrays, respectively. e Median methylation (β) across all UGT1A exons decreases in siRNA-treated cells, but shows gains in all shRNA lines. f Methylation at UGT1A2 during the transient KD and recovery experiment shown in Fig. 7h, i; differences are significant between control (Scr) and d4, but not Scr versus d36. g Model for methylation changes which occurred over time following chronic (shRNA) depletion of DNMT1: while polycomb-marked regions (purple) resisted remethylation, most regions (“other”, red) regained normal or near-normal levels, while poised promoters (green) tended to become hypermethylated