library_construction_protocol: DNA was extracted and purified using Quick DNA/RNA Magbead Kit (Zymo, USA) following the manufacturer's instructions and eluted in UltraPure distilled water (Thermofisher, U.S). Post-bisulphite adaptor tagging (PBAT) strategy was performed as described, Nucleic Acids Res (2012)[Miura F et al. Amplification-free whole-genome bisulfite sequencing by post-bisulfite adaptor tagging (2012)]. Briefly, DNA purified from treated cells underwent bisulphite conversion using the EZ-96 DNA Methylation-Direct MagPrep Kit (Zymo Research, U.S.; #D5044).Samples were then resuspended in a pre-amplification mix: 1X blue buffer, 0.4mM dNTP mix, 2uM 6NF preamplification oligo (5'-CTACACGACGCTCTTCCGATCTNNNNNN-3'), and UltraPure distilled water, and incubated at 65oC to denature the DNA. Klenow (3'  5' exo-, 50U) (Custom Science, AUS) was added to each sample and first strand synthesis was performed by incubating as follows: 5min at 4oC, 37 repeats of +1oC every 15s, 30min at 37oC. Samples were then incubated with Exonuclease I (40U) (New England Biolabs, U.S) at 37oC for 1 hour and purified using Agencourt AMPure XP beads (0.8X) (Beckman Coulter, U.S.). For second strand synthesis, samples and beads were resuspended in a second-strand mixture, as indicated: 1X blue buffer, 0.4mM dNTP mix, 2uM 6NR_NEB adaptor 2 oligo (5'-CAGACGTGTGCTCTTCCGATCTNNNNNN-3') and UltraPure distilled water and incubated at 95oC for 45s. Like first strand synthesis, Klenow was added to each sample and incubated on the thermocycler using the same conditions, before a second round of purification with AMPure XP beads (0.8X). To amplify the libraries for sequencing, samples and beads were resuspended in KAPA HiFi HotStart ReadyMix (1X) (Millenium Science, AUS), which contains a DNA polymerase to amplify the DNA. Following the manufacturer's instructions, specific i7 and i5 NEBNext index pairs (5uM) (New England Biolabs, U.S) were added to each sample and incubated as follows: 1 cycle at 95oC for 2min; 6 cycles of 94oC for 80s, 65oC for 30s and 72oC for 30s; 72oC for 3min; hold at 4oC. Amplified libraries were purified using AMPure XP beads (0.8X) and eluted in UltraPure distilled water. Sequencing was performed using a MiSeq Reagent Kit v2 (Illumina, U.S.) in 150bp paired-end mode, with a loading sample concentration of 10pM and a 5% PhiX (Illumina, U.S.) spike-in.