Covalent Modification of DNA Regulates Memory Formation

Abstract

(Neuron 53, 857–869; March 15, 2007) We have discovered an inadvertent error in our manuscript. We examined the methylation status and mRNA levels of the beta isoform of PP1's catalytic subunit. Regrettably, in three places within the Experimental Procedures section and in Figure 3A, this catalytic subunit isoform was labeled as gamma. This does not alter the results or their interpretation. To date, no studies on long-term memory have discriminated between PP1's different subunits or isoforms, and there is nearly 90% amino acid sequence homology between the four isoforms (α, β, γ1, and γ2) of PP1's catalytic subunit (Luo et al., 2007). We apologize for our error and any inconvenience it may have caused. Luo, W., Peterson, A., Garcia, B.A., Coombs, G., Kofahl, B., Heinrich, R., Shabanowitz, J., Hunt, D.F., Yost, H.J., and Virshup, D.M. (2007). Protein phosphatase 1 regulates assembly and function of the beta-catenin degradation complex. EMBO 26, 1511–1521. Covalent Modification of DNA Regulates Memory FormationMiller et al.NeuronMarch 15, 2007In BriefDNA methylation is a covalent chemical modification of DNA catalyzed by DNA methyltransferases (DNMTs). DNA methylation is associated with transcriptional silencing and has been studied extensively as a lifelong molecular information storage mechanism put in place during development. Here we report that DNMT gene expression is upregulated in the adult rat hippocampus following contextual fear conditioning and that DNMT inhibition blocks memory formation. In addition, fear conditioning is associated with rapid methylation and transcriptional silencing of the memory suppressor gene PP1 and demethylation and transcriptional activation of the synaptic plasticity gene reelin, indicating both methyltransferase and demethylase activity during consolidation. Full-Text PDF Open Archive