Epigenetics: Perceptive enzymes

Adding methyl groups to DNA is a way of regulating some genes and genomic sequences. Structural analysis reveals that the enzyme complex that mediates this process shows unexpected sequence specificity.

Imprinted genes are a small but developmentally important set of genes whose expression depends on the parent from which they are inherited. So, for some of these genes only the maternally inherited copy is expressed, and for others only the copy inherited from the father is expressed. Such selective gene expression is regulated by selective addition of methyl groups to the two equivalent parental chromosomes during the development of gametes (eggs and sperm); these chemical marks are then propagated in the resulting offspring1. In vertebrates, methylation of DNA, which is usually associated with the shut-down of local gene expression, is mediated by DNA methyltransferase enzymes. A question that has puzzled researchers is how these enzymes discriminate between different sequences within the genome. On page 248 of this issue, Jia et al.2 provide some clues, reporting that DNA methyltransferases show remarkable sequence specificity.