For the global epigenomic comparisons, we defined DMRs using the Lister et al method107, combining all differentially methylated sites within 250bp of one another into a single DMR and excluded any DMR with less than 3 DMSs. For each DMR in each sample, we computed its average methylation level, weighted by the number of reads overlapping it108. This resulted in a methylation level matrix with rows of DMRs and columns of samples.