Global epigenomic reconfiguration during mammalian brain development.

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Publication Year:
2013
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
PubMed ID:
23828890
Funding Grants:
Public 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. Last, 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.
Scientific 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. Last, 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.