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Science. 2013 Aug 9;341(6146):1237905. doi: 10.1126/science.1237905. Epub 2013 Jul 4.

Global epigenomic reconfiguration during mammalian brain development.

Author information

1
Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
2
Plant Energy Biology [Australian Research Council Center of Excellence (CoE)] and Computational Systems Biology (Western Australia CoE), School of Chemistry and Biochemistry, The University of Western Australia, Perth, WA 6009, Australia.
3
Computational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
4
La Jolla Institute for Allergy and Immunology and Sanford Consortium for Regenerative Medicine, La Jolla, CA 92037, USA.
5
Department of Psychiatry, Columbia University and The New York State Psychiatric Institute, New York, NY 10032, USA.
6
Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
7
Bioinformatics Program, University of California at San Diego, La Jolla, CA 92093, USA.
8
Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA.
9
Cancer Epigenetics Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona 08907, Spain.
10
Department of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
11
InstitucióCatalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain.
12
Division of Biological Sciences, University of California at San Diego, La Jolla, CA 92037, USA.
13
Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
#
Contributed equally

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.

Comment in

PMID:
23828890
PMCID:
PMC3785061
DOI:
10.1126/science.1237905
[Indexed for MEDLINE]
Free PMC Article

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