New publication in "J. Mol. Biol."

DNA methyltransferases are essential enzymes in higher eukaryotes. Importantly they interact with their target DNA sequences embedded into variable sequence context. This leads to strong and not well-understood effects of the flanking sequences on their activity and specificity. This review describes a novel "deep enzymology" technology to characterize the flanking sequence preferences of DNMTs that has been developed in the department of biochemistry. In this method, the influence of sequences flanking the methylation sites is studied by using substrates with partly randomized sequences and investigation of their methylation levels. The approach has led to the discovery of interesting and novel mechanistic findings, including the striking observation that flanking dependent methylation patters in human cells match to the in vitro preferences of the DNMTs. Moreover, it also allows investigating other mechanistic details, like the preferences of DNMTs for co-methylation of CpG sites in a certain distance.