The three SUVH proteins possess different mDNA binding preferences. (A) Schematic model of CHG methylated DNA during replication. CAG/GTC DNA generates CAG/GTC and CAG/GTC replication products which can be directly recognized by SUVH proteins (Left). CCG/GGC DNA could yield CCG/GGC and CCG/GGC replication products, which are methylated by MET1 to generate CG methylation and then serve as binding targets for the SUVH protein (Right). (B–D) Binding curves between different methylated DNAs and KYP (B), SUVH5 (C), and SUVH6 (D) measured by MST. Data points are shown as means ± SD (n = 3). Curves indicate the calculated fits according to the data points, and the binding affinities (Kd) are listed in the boxes below the binding curves. DNA sequences can be found in SI Appendix, Table S2. C marked in red in the sequence indicates 5mC. NDB, no detectable binding.