Evidence That DNA (Cytosine-5) Methyltransferase Regulates Synaptic Plasticity in the Hippocampus*
By J. Levenson, T. Roth, F. Lubin, Courtney A. Miller, I-Chia Huang, P. Desai, Lauren M. Malone, D. Sweatt. Journal of Biological Chemistry, 2006
607 citations recorded by the source corpus.
DNA (cytosine-5) methylation represents one of the most widely used mechanisms of enduring cellular memory. Stable patterns of DNA methylation are established during development, resulting in creation of persisting cellular phenotypes. There is growing evidence that the nervous system has co-opted a number of cellular mechanisms used during development to subserve the formation of long term memory. In this study, we examined the role DNA (cytosine-5) methyltransferase (DNMT) activity might play in regulating the induction of synaptic plasticity. We found that the DNA within promoters for reelin and brain-derived neurotrophic factor, genes implicated in the induction of synaptic plasticity in the adult hippocampus, exhibited rapid and dramatic changes in cytosine methylation when DNMT activity was inhibited. Moreover, zebularine and 5-aza-2-deoxycytidine, inhibitors of DNMT activity, blocked the induction of long term potentiation at Schaffer collateral synapses. Activation of protein kinase C in the hippocampus decreased reelin promoter methylation and increased DNMT3A gene expression. Interestingly, DNMT activity is required for protein kinase C-induced increases in histone H3 acetylation. Considered together, these results suggest that DNMT activity is dynamically regulated in the adult nervous system and that DNMT may play a role in regulating the induction of synaptic plasticity in the mature CNS.
Subfields: Cognitive Neuroscience, Genetics, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/fa4ee9a38766482988639a8d3d6e60214bca6bb4
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Cognitive Neuroscience
- C. Alberini
- John H. Morrison
- J. Sweatt
- E. Nestler
- Terrence J. Sejnowski
- Alcino J. Silva
- F. Lubin
- T. Roth
In Genetics
In Molecular Biology
Citations in the corpus
- Covalent modification of DNA regulates memory formation. (2007, positive): “…structure serves as an important control mechanism in memory-associated transcriptional regulation (Swank and Sweatt, 2001; Guan et al., 2002; Huang et al., 2002; Levenson et al., 2004a, 2006; Korzus et al., 2004; Alarcon et al., 2004; Wood et al., 2005; Kumar et al., 2005; Chwang et al., 2006).”
- Epigenetic regulation in psychiatric disorders (2007, background): “Other examples of rapidly reversible changes in DNA methylation in the adult brain have been reported in learning and memor”
- Dnmt3a regulates emotional behavior and spine plasticity in the nucleus accumbens (2010, background): “Pharmacological inhibition of DNA methylation blocks long-term potentiation in hippocampu”
- Epigenetic transmission of the impact of early stress across generations. (2010, neutral): “(15) (see upplement, 1 Supplementary Methods).”
- DNA Methylation and Its Basic Function (2013, methodology): “The first model utilizes pharmacological inhibitors such as 5-aza-2 0 -deoxycytadine, zebularine, or RG108 injected into the brain to impair Dnmt activity (Levenson et al, 2006; Miller and Sweatt, 2007; Miller et al, 2010).”
- EPIGENETIC REGULATION OF BDNF GENE TRANSCRIPTION IN THE CONSOLIDATION OF FEAR MEMORY (2008, background): “Recent studies suggest that DNA methylation is a crucial mechanism for controlling chromatin remodeling in the adult mammalian nervous system (Levenson et al., 2006; Nelson et al., 2008).”
- Transcription Factors in Long-Term Memory and Synaptic Plasticity (2009, positive): “Such blockage also disrupts the induction of LTP at Schaffer collateral synapses (139).”
- Dnmt1 and Dnmt3a are required for the maintenance of DNA methylation and synaptic function in adult forebrain neurons (2010, background): “Recently, studies with Dnmt inhibitors in in vitro brain slices or hippocampus in vivo”
- Global Epigenomic Reconfiguration During Mammalian Brain Development (2013, background): “Similarly, DHS sites unique to adult frontal cortex rarely overlap Adult>Fetal CG-DMRs.”
- Is folic acid good for everyone? (2008, result): “Such a conclusion is supported by the finding that DNA methyltransferase is expressed in cortical GABAergic neurons (169) and that inhibition of DNA methyltransferase leads to decreased methylation of specific CpG islands in the promoter regions of the genes for reelin and for brain-derived neurotro”