Five micrograms of genomic DNA was extracted from frozen cell pellets using the DNeasy Mini Kit (Qiagen) and spiked with 25 ng unmethylated Lambda cl857 Sam7 DNA (Promega). The DNA was fragmented with a Covaris S2 (Covaris) to 75–175 bp or 100–400 bp for single-read or paired-read libraries, respectively, followed by end repair and addition of a 39 A base. Cytosine-methylated adapters provided by Illumina were ligated to the sonicated DNA as per the manufacturer's instructions for genomic DNA library construction. For single-read libraries, adaptor-ligated DNA was isolated by two rounds of purification with AMPure XP beads (Beckman Coulter Genomics). For paired-read libraries, adaptor-ligated DNA of 275–375 bp (150–250 bp insert) was isolated by 2% agarose gel electrophoresis. Adaptor-ligated DNA (≤450 ng) was subjected to sodium bisulphite conversion using the MethylCode kit (Life Technologies) as per the manufacturer's instructions. The bisulphite-converted, adaptor-ligated DNA molecules were enriched by 4–8 cycles of PCR with the following reaction composition: 2.5 U of uracil-insensitive PfuTurboCx Hotstart DNA polymerase (Stratagene), 5 μl 10× PfuTurbo reaction buffer, 31 μM dNTPs, 1 μl Primer 1, 1 μl
