ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2020
Synaptic control of DNA methylation involves activity-dependent degradation of DNMT3A1 in the nucleus.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 30 citations in OpenAlex.
- Epigenetic Regulation of Inflammation by Dopamine in Primary Human Macrophages.bioRxiv : the preprint server for biology · 2026Article
- Epigenetic regulation of inflammation by dopamine in primary human macrophages.Frontiers in immunology · 2026Article
- A comprehensive review on adaptive plasticity and recovery mechanisms post-acquired brain injury.Neuroprotection (Chichester, England) · 2025Review
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- DNA Methylation in Long-Term Memory.Physiology (Bethesda, Md.) · 2025Review
- Review
- Dnmt3a1 regulates hippocampus-dependent memory via the downstream target Nrp1.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Epigenetic modifications of DNA and RNA in Alzheimer's disease.Frontiers in molecular neuroscience · 2024Review
- Article
- Neddylation-dependent protein degradation is a nexus between synaptic insulin resistance, neuroinflammation and Alzheimer's disease.Translational neurodegeneration · 2022Article
- Role of DNMTs in the Brain.Advances in experimental medicine and biology · 2022Review
- Neuronal activity regulates the nuclear proteome to promote activity-dependent transcription.The Journal of cell biology · 2021Article
- DNA Methyltransferase 1 (DNMT1) Shapes Neuronal Activity of Human iPSC-Derived Glutamatergic Cortical Neurons.International journal of molecular sciences · 2021Article
- Roles of N-Methyl-D-Aspartate Receptors (NMDARs) in Epilepsy.Frontiers in molecular neuroscience · 2021Review
- Mitochondrial DNA copy number can influence mortality and cardiovascular disease via methylation of nuclear DNA CpGs.Genome medicine · 2020Article
- Review
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Authors and funding
11 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA methylation is a crucial epigenetic mark for activity-dependent gene expression in neurons. Very little is known about how synaptic signals impact promoter methylation in neuronal nuclei. In this study we show that protein levels of the principal de novo DNA-methyltransferase in neurons, DNMT3A1, are tightly controlled by activation of N-methyl-D-aspartate receptors (NMDAR) containing the GluN2A subunit. Interestingly, synaptic NMDARs drive degradation of the methyltransferase in a neddylation-dependent manner. Inhibition of neddylation, the conjugation of the small ubiquitin-like protein NEDD8 to lysine residues, interrupts degradation of DNMT3A1. This results in deficits in promoter methylation of activity-dependent genes, as well as synaptic plasticity and memory formation. In turn, the underlying molecular pathway is triggered by the induction of synaptic plasticity and in response to object location learning. Collectively, the data show that plasticity-relevant signals from GluN2A-containing NMDARs control activity-dependent DNA-methylation involved in memory formation.
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