Global epigenomic reconfiguration during mammalian brain development

Science. 2013 Aug 9;341(6146):1237905. doi: 10.1126/science.1237905. Epub 2013 Jul 4.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 5-Methylcytosine / metabolism
  • Adult
  • Animals
  • Base Sequence
  • Conserved Sequence
  • Cytosine / analogs & derivatives*
  • Cytosine / metabolism
  • DNA Methylation*
  • Epigenesis, Genetic*
  • Epigenomics
  • Frontal Lobe / growth & development*
  • Gene Expression Regulation, Developmental*
  • Genome-Wide Association Study
  • Humans
  • Longevity
  • Mice
  • Mice, Inbred C57BL
  • X Chromosome Inactivation / genetics

Substances

  • 5-hydroxymethylcytosine
  • 5-Methylcytosine
  • Cytosine

Associated data

  • GEO/GSE47966