Exposing the DNA Methylome Iceberg

DNA methylation was the first epigenetic modification discovered. Until recently, comprehensive coverage of the composition and distribution of methylated cytosines across the genome was lacking. Technological advances, however, are providing methylation maps that can reveal the genomic distribution of DNA methylation in different cell states or phenotypes. The emerging picture includes extensive gene body methylation that is highly conserved in eukaryotes, the presence of DNA methylation in previously unappreciated sequence contexts, and the discovery of another modified DNA base, 5-hydroxymethylcytosine. These new data point to the role of DNA methylation both in gene silencing and gene activation; reconciliation of these seemingly contradictory roles will be essential to fully unravel the biological function of DNA methylation in eukaryotes. Here we review how these recently exposed features of the DNA methylome are challenging previously held dogmas in the field.