期刊
SCIENCE
卷 341, 期 6146, 页码 629-+出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1237905
关键词
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资金
- European Commission [LSHM-CT-2004-503039]
- National Institutes of Mental Health [MH094670]
- Howard Hughes Medical Institute
- Gordon and Betty Moore Foundation [GMBF3034]
- NIH [HG006827, AI44432, HD065812, CA151535]
- California Institute of Regenerative Medicine [RM-01729]
- Leukemia and Lymphoma Society [TRP 6187-12]
- Australian Research Council
- Government of Western Australia
- Center for Theoretical Biological Physics, University of California San Diego
- NIH (National Institute of Neurological Diseases and Stroke) [K99NS080911]
- NSF
- ICREA Funding Source: Custom
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.
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