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Global Epigenomic Reconfiguration During Mammalian Brain Development.

Global Epigenomic Reconfiguration During Mammalian Brain Development. Science (New York, N.Y.) Lister, R., Mukamel, E. A., Nery, J. R., Urich, M., Puddifoot, C. A., Johnson, N. D., Lucero, J., Huang, Y., Dwork, A. J., Schultz, M. D., Yu, M., Tonti-Filippini, J., Heyn, H., Hu, S., Wu, J. C., Rao, A., Esteller, M., He, C., Haghighi, F. G., Sejnowski, T. J., Behrens, M. M., Ecker, J. R. 2013

Abstract

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. Finally, 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.

View details for DOI 10.1126/science.1237905

View details for PubMedID 23828890