Global epigenomic reconfiguration during mammalian brain development.

TitleGlobal epigenomic reconfiguration during mammalian brain development.
Publication TypeJournal Article
Year of Publication2013
AuthorsLister 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 Published2013 Aug 9
Keywords5-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.

PubMed URL
Alternate JournalScience
PubMed ID23828890