Global Epigenomic Reconfiguration During Mammalian Brain Development

Ryan Lister(Salk Institute for Biological Studies), Eran A. Mukamel(Salk Institute for Biological Studies), Joseph R. Nery(Salk Institute for Biological Studies), Mark A. Urich(Salk Institute for Biological Studies), Clare A. Puddifoot(Salk Institute for Biological Studies), Nicholas D. Johnson(Salk Institute for Biological Studies), Jacinta Lucero(Salk Institute for Biological Studies), Yun Huang(La Jolla Institute for Immunology), Andrew J. Dwork(New York Psychoanalytic Society and Institute), Matthew D. Schultz(Salk Institute for Biological Studies), Miao Yu(University of Chicago), Julian Tonti‐Filippini(ARC Centre of Excellence in Plant Energy Biology), Holger Heyn(Institut d'Investigació Biomédica de Bellvitge), Shijun Hu(Stanford University), Joseph C. Wu(Stanford University), Anjana Rao(La Jolla Institute for Immunology), Manel Esteller(Institució Catalana de Recerca i Estudis Avançats), Chuan He(University of Chicago), Fatemeh Haghighi(New York Psychoanalytic Society and Institute), Terrence J. Sejnowski(Salk Institute for Biological Studies), M. Margarita Behrens(Salk Institute for Biological Studies), Joseph R. Ecker(Salk Institute for Biological Studies)
Science
July 5, 2013
10.1126/science.1237905
Cited by 1,910Open Access
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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.

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