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      5-hmC-mediated epigenetic dynamics during postnatal neurodevelopment and aging.

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          Abstract

          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 ∼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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          Author and article information

          Journal
          Nat Neurosci
          Nature neuroscience
          Springer Science and Business Media LLC
          1546-1726
          1097-6256
          Oct 30 2011
          : 14
          : 12
          Affiliations
          [1 ] Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA.
          Article
          nn.2959 NIHMS357667
          10.1038/nn.2959
          3292193
          22037496
          b4eaf746-900a-401c-8441-28a0520c3ce4
          History

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