Journal
NATURE NEUROSCIENCE
Volume 14, Issue 12, Pages 1607-U150Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nn.2959
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Funding
- US National Institutes of Health (NIH) [T32MH087977]
- NIH [CA129831, CA129831-03S1, GM071440, GM049245, NS051630, MH076090, P50AG025688]
- Emory Alzheimer's Disease Center [P50AG025688]
- Simons Foundation Autism Research Initiative
- Beckman Young Investigator Award
- Basil O'Connor Scholar Research Award
- Emory Genetics Discovery Fund
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DNA methylation dynamics influence brain function and are altered in neurological disorders. 5-hydroxymethylcytosine (5-hmC), a DNA base that is derived from 5-methylcytosine, accounts for similar to 40% of modified cytosine in the brain and has been implicated in DNA methylation-related plasticity. We mapped 5-hmC genome-wide in mouse hippocampus and cerebellum at three different ages, which allowed us to assess its stability and dynamic regulation during postnatal neurodevelopment through adulthood. We found developmentally programmed acquisition of 5-hmC in neuronal cells. Epigenomic localization of 5-hmC-regulated regions revealed stable and dynamically modified loci during neurodevelopment and aging. By profiling 5-hmC in human cerebellum, we found conserved genomic features of 5-hmC. Finally, we found that 5-hmC levels were inversely correlated with methyl-CpG-binding protein 2 dosage, a protein encoded by a gene in which mutations cause Rett syndrome. These data suggest that 5-hmC-mediated epigenetic modification is critical in neurodevelopment and diseases.
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