Fig. 6: mPAF15Ub2 is required for the proper maintenance of DNA methylation in mouse ESCs.
From: Two distinct modes of DNMT1 recruitment ensure stable maintenance DNA methylation
a, b DNA methylation levels (%) as measured by RRBS in wild-type (WT) and Paf15 K15R/K24R (KRKR) double mutant ESCs. a Global DNA methylation levels and b CpG methylation levels at CpG islands, promoters, gene bodies, and repeats in wt and KRKR ESCs. p Values based on ANOVA with post hoc Tukey’s test. c Density plot depicting the distribution of DNA methylation levels of individual CpG sites in wt and KRKR ESCs. d–f Replication timing of hypomethylated vs. unchanged tiles in d Paf15 KRKR ESCs, e Dnmt1 KO ESCs, and f Uhrf1 KO ESCs. For comparisons between hypomethylated and unchanged tiles, Welch’s two-sided t test was used for calculating p values. Differentially methylated tiles losing DNA methylation (hypomethylated tiles) were defined as those with p < 0.05 and a methylation loss >25%; p values were derived from a methylKit package (see “Methods”). g Model of the two pathways of dual mono-ubiquitylation facilitating maintenance of DNA methylation. Both requiring UHRF1, PAF15Ub2 and H3Ub2 preferentially contribute to the DNMT1-mediated maintenance of DNA methylation of early and late replicating regions, respectively. For the boxplots in a, b, d–f, the horizontal black lines within boxes represent median values, boxes indicate the upper and lower quartiles, and whiskers indicate the 1.5× interquartile range. Source data are provided as a Source Data file.
