New publication in "Nucleic Acids Research"
In this work, we investigated details of the DNA recognition mechanism of the catalytic domain of the DNA methyltransferase DNMT3B. We identified combined effects of CpG recognition and flanking sequence interaction together with complex contact networks involved in balancing the interaction of DNMT3B with different flanking sites. By the establishment of alternative interaction networks with different flanking contexts, the enzyme minimizes flanking sequence effects and is able to methylate all CpG sites with similar rates. Our data showed that non-CpG flanking preferences of DNMT3B are highly correlated with non-CpG methylation patterns in human cells. Finally, comparison of the flanking sequence preferences of human and mouse DNMT3B revealed subtle differences of the flanking sequence preferences of both enzymes suggesting that co-evolution occurred of the flanking sequence preferences of DNMTs and the sequences of their most important cellular DNMT targets.