Global epigenomic reconfiguration during mammalian brain development

DNA methylation has been implicated in mammalian brain development and plasticity underlying learning and memory. We report the genome-wide composition, patterning, cell-specificity and dynamics of DNA methylation at single-base resolution in the frontal cortex of humans and mice throughout their lifespan. We observed methylome reconfiguration occurring during development from fetal to young adult and coincident with synaptogenesis, and highly conserved non-CG methylation (mCH) accumulating in neurons, but not glia, to become the dominant form of methylation in the human neuronal genome. We also identified a mCH signature that identifies genes escaping X-chromosome inactivation in neurons and developmentally dynamic, cell-type specific differentially CG-methylated regions that are enriched at putative regulatory regions. Overall, this indicates that the mammalian brain has unique DNA methylation features that are precisely conserved, yet dynamic and cell-type specific.