DNMT3B methylates the 5 position of cytosine in DNA. DNMT3B preferentially methylates cytosine residues that have T at the -1 position and G at the +1 position (Wienholz et al. 2010). Sites methylated de novo by DNMT3B tend to be in transcriptionally inactive regions associated with histone H3 trimethylated at lysine-27 (Choi et al. 2011). Association with DNMT3L increases the processivity of DNMT3B (Van Emburgh and Robertson 2011) and increases methylation at sites that would have low methylation by the activity of DNMT3B alone (Wienholz et al. 2010). Interaction of DNMT3L with DNMT3B-isoform2 stimulates methylation activity significantly (Van Emburgh and Robertson 2011), but interaction of DNMT3L with DNMT3B-isoform1 has little effect on methylation activity (Chedin et al. 2002, Van Emburgh and Robertson 2011). Methylation in embryos but not in gametes (oocytes and spermatozoa) requires DNMT3B (Okano et al. 1999, Kaneda et al. 2004, Borgel et al. 2010, Kaneda et al. 2010).