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The methylation of DNA in mammalian genomes regulates gene expression, guiding differentiation and maintaining cellular identity within tissues. However, it may have a distinct function in the brain. On page 629 of this issue, Lister et al. (1) present a comprehensive analysis of DNA methylation and hydroxymethylation at single-base resolution in the mammalian frontal cortex. The authors chart out striking postnatal alterations in neuronal methylation profiles that occur as synapses develop and are refined, from the fetal to adult stage. The patterns suggest that DNA methylation is important in the maturation of neurons in the developing brain.