Authors:
Ryan Lister, Eran A. Mukamel, Joseph R. Nery, Mark Urich, Clare A. Puddifoot, Nicholas D. Johnson, Jacinta Lucero, Yun Huang, Andrew J. Dwork, Matthew D. Schultz, Miao Yu, Julian Tonti-Filippini, Holger Heyn, Shijun Hu, Joseph C. Wu, Anjana Rao, Manel Esteller, Chuan He, Fatemeh G. Haghighi, Terrence J. Sejnowski, M. Margarita Behrens, & Joseph R. Ecker
Summary:
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.
Source:
Science; (07/04/13)