Stably inherited DNA hemimethylation regulates chromatin interaction and transcription DNA methylation is an essential epigenetic modification that regulates gene transcription, embryonic development, and cell differentiation in both animals and plants. In mammals, DNA methylation generally occurs at CpG dinucleotides in a symmetric fashion ( 1 ), meaning that if a cytosine (C) residue on one CpG is methylated, the corresponding residue on the complementary strand will be too. This pattern temporarily breaks down during DNA replication, when the unmethylated daughter (nascent) strand and the methylated parent strand create an asymmetrically methylated CpG dyad termed hemimethylated DNA. It was thought that the destiny of hemimethylated DNA was to become fully methylated or unmethylated by replication-coupled dilution. However, about 10% of CpGs in embryonic stem cells (ESCs) ( 1 ) and trophoblast stem cells ( 2 ) remain hemimethylated. It is not known if this unusual hemimethylation signature occurs by chance or by design. On page 1166 of this issue, Xu and Corces ( 3 ) reveal that some CpGs in the genome can be hemimethylated by design. Intriguingly, they found that hemimethylated sites are inherited over several cell divisions. This challenges the prevailing view that hemimethylation is transient and suggests that this DNA modification could be maintained as a stable epigenetic state.