<i>Dnmt3a</i> knockout in excitatory neurons impairs postnatal synapse maturation and increases the repressive histone modification H3K27me3.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 35604009.
- Also identified by DOI 10.7554/eLife.66909 and PMC identifier 9170249.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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 <i>Dnmt3a</i> 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 <i>Dnmt3a</i> 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.
Medical subject headings
- DNA Methyltransferase 3A
- Histone Code
- Neurons
- Synapses