RRBS was performed on 500 ng of genomic DNA for all cell lines as previously described (Gu et al., 2010). All libraries have been sequenced to an average of 1,500,000 individual CpG per sample at a genomic coverage of 5× or higher. Raw reads were mapped using Bismark (Krueger and Andrews, 2011), and methylation calling was performed using a custom method. Methylation analysis, unsupervised hierarchical clustering, PCA, and pairwise comparisons were performed using MethylKit. Differential methylation was calculated using Fisher's exact test. A cutoff of 25% was applied based on a difference in methylation level. p Values were adjusted using SLIM method and a cutoff of FDR ≤ 0.01 was applied. Genomic annotation was performed using Homer annotation (Heinz et al., 2010). Data analysis was performed with the R statistics package (http://www.r-project.org/). RRBS data are available in the ArrayExpress database (www.ebi.ac.uk/arrayexpress) under accession number E-MTAB-3859.
