DNA was purified using phenol-chlorofom extraction protocol. Briefly,90 ng from naïve hESCs were digested with LpnPI (New England Biolabs) generating 32 bp fragments around the fully methylated recognition site containing a CpG. These short DNA fragments were further processed using the ThruPlex DNA–seq 96D kit (Rubicon Genomics Ann Arbor). Stem-loop adapters were blunt-end ligated to repaired input DNA and amplified to include dual indexed barcodes using a high-fidelity polymerase to generate an indexed Illumina NGS library. The amplified end product was purified on a Pippin HT system with 3% agarose gel cassettes (Sage Science).