Two epigenetic pathways of transcriptional repression, DNA methylation and polycomb repressive complex 2 (PRC2), are known to regulate neuronal development and function. However, their respective contributions to brain maturation are unknown. We found that conditional loss of the de novo DNA methyltransferase Dnmt3a in mouse excitatory neurons altered expression of synapse-related genes, stunted synapse maturation, and impaired working memory and social interest. At the genomic level, loss of Dnmt3a abolished postnatal accumulation of CG and non-CG DNA methylation, leaving adult neurons with an unmethylated, fetal-like epigenomic pattern at ~222,000 genomic regions. The PRC2-associated histone modification, H3K27me3, increased at many of these sites. Our data support a dynamic interaction between two fundamental modes of epigenetic repression during postnatal maturation of excitatory neurons, which together confer robustness on neuronal regulation.
Rosa Gomez-Castanon合作论文数1Jun-Hao Li合作论文数1Julia K Osteen合作论文数1Jacinta Lucero合作论文数1
Eran Mukamel合作论文数Halicioglu Data Science Institute, University of California, San Diego1Yan Pang合作论文数1
Linjing Fang合作论文数Salk Inst Biol Studies, Waitt Adv Biophoton Ctr, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA1
Michael S Cuoco合作论文数Klarman Cell Observ, Broad Inst MIT & Harvard1
Chongyuan Luo合作论文数Luo lab, Department of Human Genetics, University of California, Los Angeles;David Geffen School of Medicine, University of California, Los Angeles1
Antonio Pinto-Duarte合作论文数Howard Hughes Medical Institute, Salk Institute for Biological Studies;Institute of Pharmacology and Neurosciences, University of Lisbon;Institute of Molecular Medicine, University of Lisbon;University of Lisbon, University of Lisbon1
Chi-Yu Lai合作论文数College of Public Health, National Taiwan University1
Joseph Nery合作论文数Genomic Analysis Laboratory, Salk Institute for Biological Studies1
Zander Mark合作论文数1
Joseph Ecker合作论文数Howard Hughes Medical Institute;The Salk Institute for Biological Studies1Susan B. Powell合作论文数1
Terrence Sejnowski合作论文数Department of Neurobiology, School of Biological Sciences, University of California, San Diego;Howard Hughes Medical Institute;The Salk Institute for Biological Studies1M. Margarita Behrens合作论文数Division of Geriatrics;Department of Medicine;University of California at San Diego;Department of Biology;Volen Center for Complex Systems;Brandeis University;University of California at San Diego, Brandeis University1
