TY - JOUR
T1 - Global epigenomic reconfiguration during mammalian brain development
AU - Lister, Ryan
AU - Mukamel, Eran A.
AU - Nery, Joseph R.
AU - Urich, Mark
AU - Puddifoot, Clare A.
AU - Johnson, Nicholas D.
AU - Lucero, Jacinta
AU - Huang, Yun
AU - Dwork, Andrew J.
AU - Schultz, Matthew D.
AU - Yu, Miao
AU - Tonti-Filippini, Julian
AU - Heyn, Holger
AU - Hu, Shijun
AU - Wu, Joseph C.
AU - Rao, Anjana
AU - Esteller, Manel
AU - He, Chuan
AU - Haghighi, Fatemeh G.
AU - Sejnowski, Terrence J.
AU - Behrens, M. Margarita
AU - Ecker, Joseph R.
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84879663784
U2 - 10.1126/science.1237905
DO - 10.1126/science.1237905
M3 - Article
C2 - 23828890
AN - SCOPUS:84879663784
SN - 0036-8075
VL - 341
JO - Science
JF - Science
IS - 6146
M1 - 1237905
ER -