MethylC-seq library generation was performed as described previously (Ulrich et al, 2015; Nature Protocols). Briefly, the genomic DNA was sonicated to an average size of 200 bp using a Covaris sonicator. Sonicated DNA was then purified and end-repaired followed by the ligation of methylated Illumina TruSeq sequencing adapters. Library amplification was performed with KAPA HiFi HotStart Uracil+ DNA polymerase (Kapa Biosystems, Woburn, MA), using 6 cycles of amplification.