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

First Author  Szulwach KE Year  2011
Journal  Nat Neurosci Volume  14
Issue  12 Pages  1607-16
PubMed ID  22037496 Mgi Jnum  J:180327
Mgi Id  MGI:5306102 Doi  10.1038/nn.2959
Citation  Szulwach KE, et al. (2011) 5-hmC-mediated epigenetic dynamics during postnatal neurodevelopment and aging. Nat Neurosci 14(12):1607-16
abstractText  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 approximately 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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