ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2008
Activity-dependent suppression of miniature neurotransmission through the regulation of DNA methylation.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 papers.
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Who cites it
142 citing papers in PubMed, 248 citations in OpenAlex.
- DREAMS illuminates spatial DNA and RNA modification landscapes.Nature cell biology · 2026Article
- Methylation Mesa define functional regulatory elements for targeted gene activation.Nature communications · 2026Article
- DNA methylation regulates the extinction of fear memory.World journal of psychiatry · 2025Article
- Review
- Delving Into the Interaction Between Exercise and Diabetes on Methylation of the FKBP5 Gene.Journal of diabetes research · 2025Article
- Insights into epileptogenesis from post-traumatic epilepsy.Nature reviews. Neurology · 2024Review
- Brain-derived neurotrophic factor scales presynaptic calcium transients to modulate excitatory neurotransmission.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Abnormal DNA methylation within HPA-axis genes years after paediatric critical illness.Clinical epigenetics · 2024Article
- Differential usage of DNA modifications in neurons, astrocytes, and microglia.Epigenetics & chromatin · 2023Article
- Developmental and epileptic encephalopathies: from genetic heterogeneity to phenotypic continuum.Physiological reviews · 2023Review
- The computational power of the human brain.Frontiers in cellular neuroscience · 2023Review
- The Role of DNA Methylation in Stroke Recovery.International journal of molecular sciences · 2022Review
- MeCP2 loss-of-function dysregulates microRNAs regionally and disrupts excitatory/inhibitory synaptic transmission balance.Hippocampus · 2022Article
- Long-Term Treatment with Bortezomib Induces Specific Methylation Changes in Differentiated Neuronal Cells.Cancers · 2022Article
- Post-Traumatic Epilepsy and Comorbidities: Advanced Models, Molecular Mechanisms, Biomarkers, and Novel Therapeutic Interventions.Pharmacological reviews · 2022Review
- Inhibitors of DNA Methylation.Advances in experimental medicine and biology · 2022Review
- Neuronal activation modulates enhancer activity of genes for excitatory synaptogenesis through de novo DNA methylation.The Journal of reproduction and development · 2021Article
- Influence ofGenes · 2021Article
- A subthreshold synaptic mechanism regulating BDNF expression and resting synaptic strength.Cell reports · 2021Article
- Environmental enrichment preserves a young DNA methylation landscape in the aged mouse hippocampus.Nature communications · 2021Article
82 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA methylation is an epigenetic mechanism that plays a critical role in the repression of gene expression. Here, we show that DNA methyltransferase (DNMT) inhibition in hippocampal neurons results in activity-dependent demethylation of genomic DNA and a parallel decrease in the frequency of miniature EPSCs (mEPSCs), which in turn impacts neuronal excitability and network activity. Treatment with DNMT inhibitors reveals an activity-driven demethylation of brain-derived neurotrophic factor promoter I, which is mediated by synaptic activation of NMDA receptors, because it is susceptible to AP-5, a blocker of NMDA receptors. The specific effect of DNMT inhibition on spontaneous excitatory neurotransmission requires gene transcription and is occluded in the absence of the transcriptional repressor methyl-CpG-binding protein 2 (MeCP2). Interestingly, enhancing excitatory activity, in the absence of DNMT inhibitors, also produces similar decreases in DNA methylation and mEPSC frequency, suggesting a role for DNA methylation in the control of homeostatic synaptic plasticity. Furthermore, adding excess substrate for DNA methylation (S-adenosyl-L-methionine) rescues the suppression of mEPSCs by DNMT inhibitors in wild-type neurons, as well as the defect seen in MeCP2-deficient neurons. These results uncover a means by which NMDA receptor-mediated synaptic activity drives DNA demethylation within mature neurons and suppresses basal synaptic function.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.