Global epigenomic reconfiguration during mammalian brain development.
|Title||Global epigenomic reconfiguration during mammalian brain development.|
|Publication Type||Journal Article|
|Year of Publication||2013|
|Authors||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|
|Date Published||2013 Aug 9|
|Keywords||5-Methylcytosine, Adult, Animals, Base Sequence, Conserved Sequence, Cytosine, DNA Methylation, Epigenesis, Genetic, Epigenomics, Frontal Lobe, Gene Expression Regulation, Developmental, Genome-Wide Association Study, Humans, Longevity, Mice, Mice, Inbred C57BL, X Chromosome Inactivation|
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.