Global epigenomic reconfiguration during mammalian brain development.

Global epigenomic reconfiguration during mammalian brain development.
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哺乳动物大脑发育过程中的全球表观基因组重新配置。

DOI:
10.1126/science.1237905
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发表时间:
2013-08-09
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Ecker JR
Ecker JR
中科院分区:
其他
文献类型:
--
作者:
Lister R;Mukamel EA;Nery JR;Urich M;Puddifoot CA;Johnson ND;Lucero J;Huang Y;Dwork AJ;Schultz MD;Yu M;Tonti-Filippini J;Heyn H;Hu S;Wu JC;Rao A;Esteller M;He C;Haghighi FG;Sejnowski TJ;Behrens MM;Ecker JR

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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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