Meta-Biol

• Pathways

DNMT3A methylates the 5 position of cytosine in DNA. As inferred from the mouse homolog, DNMT3A generates asymmetric methylation (methylation of only one strand) of CG dinucleotides and non-CG cytosine residues. DNMT3L interacts with and stimulates the catalytic activity of DNMT3A2 and DNMT3A (Chen et al. 2005, Kareta et al. 2006, Ooi et al. 2007, Holz-Schietinger and Reich 2010). DNMT3A preferentially methylates DNA in regions of transcriptionally active chromatin: DNMT3A-isoform1 transfected into human cells (293T cells) tended to methylate active regions of the genome that were associated with trimethylated lysine-4 of histone H3 (H4K4me3) (Choi et al. 2011). Likewise, in mouse oocytes and embryos CG islands methylated by DNMT3A tend to be located in active transcription units, but with low levels of methylated H3K4 (Smallwood et al. 2011). DNMT3A and its homologue DNMT3B have different preferences for flanking sequences of CG dinucleotides, with DNMT3A tending to methylate sites that have T at the -2 position and C at the +2 position (Wienholz et al. 2010). DNMT3L increases methylation by DNMT3A at sites that are weakly methylated by DNMT3A alone (Wienholz et al. 2010).