title: Global epigenomic reconfiguration during mammalian brain development.
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.
authors.affiliation: Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.|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.
authors.forename: Ryan
authors.initials: R
authors.lastname: Lister
authors.affiliation: Computational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Eran A
authors.initials: EA
authors.lastname: Mukamel
authors.affiliation: Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Nery
authors.affiliation: Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Urich
authors.affiliation: Computational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Clare A
authors.initials: CA
authors.lastname: Puddifoot
authors.affiliation: Computational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Johnson
authors.affiliation: Computational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Jacinta
authors.initials: J
authors.lastname: Lucero
authors.affiliation: La Jolla Institute for Allergy and Immunology and Sanford Consortium for Regenerative Medicine, La Jolla, CA 92037, USA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Psychiatry, Columbia University and The New York State Psychiatric Institute, New York, NY 10032, USA.|Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Dwork
authors.affiliation: Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.|Bioinformatics Program, University of California at San Diego, La Jolla, CA 92093, USA.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Schultz
authors.affiliation: Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Miao
authors.initials: M
authors.lastname: Yu
authors.affiliation: 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.
authors.forename: Julian
authors.initials: J
authors.lastname: Tonti-Filippini
authors.affiliation: Cancer Epigenetics Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona 08907, Spain.
authors.forename: Holger
authors.initials: H
authors.lastname: Heyn
authors.affiliation: Department of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Shijun
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Wu
authors.affiliation: La Jolla Institute for Allergy and Immunology and Sanford Consortium for Regenerative Medicine, La Jolla, CA 92037, USA.
authors.forename: Anjana
authors.initials: A
authors.lastname: Rao
authors.affiliation: Cancer Epigenetics Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona 08907, Spain.|InstitucióCatalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain.
authors.forename: Manel
authors.initials: M
authors.lastname: Esteller
authors.affiliation: Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Chuan
authors.initials: C
authors.lastname: He
authors.affiliation: Department of Psychiatry, Columbia University and The New York State Psychiatric Institute, New York, NY 10032, USA.
authors.forename: Fatemeh G
authors.initials: FG
authors.lastname: Haghighi
authors.affiliation: Computational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.|Division of Biological Sciences, University of California at San Diego, La Jolla, CA 92037, USA.|Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Terrence J
authors.initials: TJ
authors.lastname: Sejnowski
authors.affiliation: Computational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: M Margarita
authors.initials: MM
authors.lastname: Behrens
authors.affiliation: Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.|Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Ecker
mesh_terms: D044503:5-Methylcytosine / Q000378:metabolism / Q000031:analogs & derivatives; D000328:Adult; D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence; D003596:Cytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D057890:Epigenomics; D005625:Frontal Lobe / Q000254:growth & development*; D018507:Gene Expression Regulation, Developmental; D055106:Genome-Wide Association Study; D006801:Humans; D008136:Longevity; D051379:Mice; D008810:Mice, Inbred C57BL; D049951:X Chromosome Inactivation / Q000235:genetics
chemical_list: C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine