Mammalian DNA Methyltransferase Structural Themes

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. The DNA methyltransferases (Dnmts) 1, 3a, and the protein factors Dnmt3L and UHRF1 are required, respectively, for de novo and maintenance methylation. Recent data demonstrated that the mammalian genomes also contain 5-hydroxymethylcytosine, enzymatically converted from 5-methylcytosine, suggesting that the DNA methylation is regulated in mammalian cells via enzymatic conversion. Given their importance, many basic questions remain to be answered about the proteins responsible for DNA methylation and hydroxymethylation, and for coordination with the parallel histone-modification system.