Figure 2. Dnmt5 mediates symmetrical CG methylation.

(A) Fractional CG methylation is shown with Tukey’s running median smoothing across chromosome 10. The positions of TEs are shown as black vertical lines at the top. Further analyses of TEs are in Figure S2B. Data are shown for wild-type genomic DNA grown and prepared at ATCC (WT) and the DNMT5-deleted strain we grew (dnmt5Δ). We also grew a control “wild-type” strain (WT47, a deletion of the unrelated gene SXI1), constructed with the same procedure as the strain with deletion of DNMT5 (Liu et al., 2008), to ensure that the absence of methylation in dnmt5Δ was not an artifact of the strain construction process or growth conditions. This also allows assessment of the reproducibility of our methylation data, which show strong quantitative similarity (Pearson’s r = 0.90 for the unsmoothed whole-genome data). For comparison, the data for the two WT strains are not correlated with those for the dnmt5Δ strain (Pearson’s r < 0.01 for both comparisons). (B) We analyzed the symmetry of methylation at CGCG sites genome-wide. To remove from the analysis uninformative regions where all of the cytosines are either methylated or unmethylated, we selected the CGCG sites that contain at least one cytosine with high (>85%) and one with low (<15%) methylation in the population of cells and with all cytosines having at least 10-fold sequencing coverage. For these informative sites in each species, the first bar (blue) shows the Pearson’s r of cytosines within CG sites and the second bar (orange) shows the Pearson’s r of the internal cytosines between adjacent CG sites. High-resolution examples of symmetrical methylation at CG sites are in Figure S2A.