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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

Authors

  • Lister R
  • Mukamel EA
  • Nery JR
  • Urich M
  • Puddifoot CA
  • Johnson ND
  • Lucero J
  • Huang Y
  • Dwork AJ
  • Schultz MD
  • Yu M
  • Tonti-Filippini J
  • Heyn H
  • Hu S
  • Wu JC
  • Rao A
  • Esteller M
  • He C
  • Haghighi FG
  • Sejnowski TJ
  • Behrens MM
  • Ecker JR

Journal

Science (New York, N.Y.)

Publication Data

August 9, 2013

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:

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