Dnmt3a knockout in excitatory neurons impairs postnatal synapse maturation and increases the repressive histone modification H3K27me3

Media type: E-Article
Title: Dnmt3a knockout in excitatory neurons impairs postnatal synapse maturation and increases the repressive histone modification H3K27me3
Contributor: Li, Junhao; Pinto-Duarte, Antonio; Zander, Mark; Cuoco, Michael S; Lai, Chi-Yu; Osteen, Julia; Fang, Linjing; Luo, Chongyuan; Lucero, Jacinta D; Gomez-Castanon, Rosa; Nery, Joseph R; Silva-Garcia, Isai; Pang, Yan; Sejnowski, Terrence J; Powell, Susan B; Ecker, Joseph R; Mukamel, Eran A; Behrens, M Margarita
Published: eLife Sciences Publications, Ltd, 2022
Published in: eLife, 11 (2022)
Language: English
DOI: 10.7554/elife.66909
ISSN: 2050-084X
Origination:
Footnote:
Description: <jats:p>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 <jats:italic>Dnmt3a</jats:italic> 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 <jats:italic>Dnmt3a</jats:italic> 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.</jats:p>
Access State: Open Access

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