The methylation of mammalian DNA, primarily at CpG dinucleotides, has long been recognized to play a major role in controlling gene expression, among other functions. Given their importance, it is surprising how many basic questions remain to be answered about the proteins responsible for this methylation and for coordination with the parallel chromatin-marking system that operates at the level of histone modification. This article reviews recent studies on, and discusses the resulting biochemical and structural insights into, the DNA nucleotide methyltransferase (Dnmt) proteins 1, 3a, 3a2, 3b, and 3L.
