DNA methylation is commonly dysregulated in a wide array of cancers, and numerous therapeutics have been developed to target this pathway. 5-Azacytidine is a DNA hypomethylating agent that can be particularly effective treatment in TET2-mutated myelodysplastic syndrome patients. The cover depicts hexagonal bins representing the density of CpG loci in a differential analysis of DNA methylation comparing targeted bisulfite sequencing data from TET2 wild-type and TET2 knockout human erythroleukemia cell lines (density gradient from red to blue, with red indicating larger number of CpG loci falling within the hexagonal bin and blue indicating a lesser number). The authors found that TET2 is essential for maintaining low levels of DNA methylation at erythroid-specific transcriptional enhancers, and that 5-Azacytidine can counteract aberrant hypermethylation of these enhancers when TET2 is mutated. For more information, see the article on page 451.