Global epigenomic reconfiguration during mammalian brain development.
DNA methylation is 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 human and mouse frontal cortex throughout their lifespan. Widespread methylome reconfiguration occurs during fetal to young adult development, coincident with synaptogenesis. During this period, highly conserved non-CG methylation (mCH) accumulates in neurons, but not glia, to become the dominant form of methylation in the human neuronal genome. Moreover, we found an mCH signature that identifies genes escaping X-chromosome inactivation. Last, whole-genome single-base resolution 5-hydroxymethylcytosine (hmC) maps revealed that hmC marks fetal brain cell genomes at putative regulatory regions that are CG-demethylated and activated in the adult brain and that CG demethylation at these hmC-poised loci depends on Tet2 activity.
Pubmed ID: 23828890 RIS Download
5-Methylcytosine | Adult | Animals | Base Sequence | Conserved Sequence | Cytosine | DNA Methylation | Epigenesis, Genetic | Epigenomics | Frontal Lobe | Gene Expression Regulation, Developmental | Genome-Wide Association Study | Humans | Longevity | Mice | Mice, Inbred C57BL | X Chromosome Inactivation