The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.
Activity-Dependent Suppression of Miniature Neurotransmission through the Regulation of DNA Methylation
Open accessAbstract
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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Cites
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Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2
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Activity-dependent scaling of quantal amplitude in neocortical neurons
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Ca2+ Influx Regulates BDNF Transcription by a CREB Family Transcription Factor-Dependent Mechanism
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DNA Methylation-Related Chromatin Remodeling in Activity-Dependent Bdnf Gene Regulation
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Cited by
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Roth, T. L., Lubin, F. D., Funk, A. J., & Sweatt, J. D. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.11.028 · Cited by 1,273
Dnmt1 and Dnmt3a maintain DNA methylation and regulate synaptic function in adult forebrain neurons
Feng, J., Zhou, Y., Campbell, S. L., Le, T., Li, E., Sweatt, J. D., Silva, A. J., & Fan, G. (2010) · Nature Neuroscience · doi:10.1038/nn.2514 · Cited by 1,019
Epigenetic Regulation of bdnf Gene Transcription in the Consolidation of Fear Memory
Lubin, F. D., Roth, T. L., & Sweatt, J. D. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.1786-08.2008 · Cited by 793
Neuronal activity modifies the DNA methylation landscape in the adult brain
Guo, J. U., Ma, D. K., Mo, H., Ball, M. P., Jang, M.-H., Bonaguidi, M. A., Balazer, J. A., Eaves, H. L., Xie, B., Ford, E., et al. (2011) · Nature Neuroscience · doi:10.1038/nn.2900 · Cited by 669
Gene–Stress–Epigenetic regulation of FKBP5: clinical and translational implications
Zannas, A. S., Wiechmann, T., Gassen, N. C., & Binder, E. B. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2015.235 · Cited by 622
Metadata
- Authors
- Nelson, E. D., Kavalali, E. T., & Monteggia, L. M.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2008-01-09
- Volume
- 28
- Issue
- 2
- Pages
- 395-406
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- OpenAlex
- W2062872787
- Cited by
- 254
- References
- 51
- FWCI
- 11.40
- Type
- journal article
- Language
- en
- Open access
- hybrid
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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