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Global epigenomic reconfiguration during mammalian brain development.

Science (New York, N.Y.) | Aug 9, 2013

http://www.ncbi.nlm.nih.gov/pubmed/23828890

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

Mesh terms: 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

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Associated grants

  • Agency: NIAID NIH HHS, Id: AI44432
  • Agency: NCI NIH HHS, Id: CA151535
  • Agency: NICHD NIH HHS, Id: HD065812
  • Agency: NHGRI NIH HHS, Id: HG006827
  • Agency: NINDS NIH HHS, Id: K99NS080911
  • Agency: NIMH NIH HHS, Id: MH094670
  • Agency: NIAID NIH HHS, Id: R01 AI044432
  • Agency: NCI NIH HHS, Id: R01 CA151535
  • Agency: NICHD NIH HHS, Id: R01 HD065812
  • Agency: NHGRI NIH HHS, Id: R01 HG006827
  • Agency: NIMH NIH HHS, Id: R01 MH094670
  • Agency: NIMH NIH HHS, Id: R01 MH094774
  • Agency: Howard Hughes Medical Institute, Id:
  • Agency: Howard Hughes Medical Institute, Id:

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