DNA methylation and demethylation are increasingly recognized as important epigenetic factors in both plants and animals. DNA methylation, which is catalyzed by DNA methyltransferases (DNMTs), is a relatively stable and heritable modification that controls gene expression, cellular differentiation, genomic imprinting, paramutation, transposon movement, X-inactivation, and embryogenesis 1. The methylation of cytosine to 5-methylcytosine (5mC) is an important example of DNA modification in animals and plants. This highlight concerns DNA demethylation mechanisms in mammals and whether they are similar to that in plants.