EZH2 Methyltransferase Activity Controls Pten Expression and mTOR Signaling during Fear Memory Reconsolidation

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Timothy J JaromeFarah D Lubin

Abstract

Memory retrieval induces a transient period of increased transcriptional and translational regulation in neurons called reconsolidation, which is regulated by the protein kinase B (AKT)-mammalian target of rapamycin (mTOR) pathway. However, it is currently unknown how activation of the AKT-mTOR pathway is regulated during the reconsolidation process. Here, we found that in male rats retrieval of a contextual fear memory transiently increased Enhancer of Zeste Homolog 2 (EZH2) levels along with increased histone H3 lysine 27 trimethylation (H3K27me3) levels, which correlated with decreased levels of phosphatase and tensin homolog (PTEN), a potent inhibitor of AKT-mTOR-dependent signaling in the hippocampus. Further experiments found increased H3K27me3 levels and DNA methylation across the Pten promoter and coding regions, indicating transcriptional silencing of the Pten gene. Pten H3K27me3 levels did not change following training or after the retrieval of a remote (old) fear memory, suggesting that this mechanism of Pten repression was specific to the reconsolidation of a new memory. In vivo siRNA-mediated knockdown of Ezh2 in the hippocampus abolished retrieval-induced increases in H3K27me3 and prevented decreases in PTEN level...Continue Reading

Citations

Dec 27, 2018·The European Journal of Neuroscience·Matthew E GloverSarah M Clinton
Dec 7, 2018·Psychopharmacology·Paul R Marshall, Timothy W Bredy
Nov 28, 2018·International Journal of Molecular Sciences·Karina Sánchez-AlegríaClorinda Arias
Jan 31, 2019·Nature Reviews. Neuroscience·Rianne R Campbell, Marcelo A Wood
Oct 2, 2019·Experimental and Therapeutic Medicine·Hao XuWeilin Wang
Dec 2, 2020·International Journal of Molecular Sciences·Shaghayegh NavabpourTimothy J Jarome
Dec 17, 2020·Learning & Memory·Andressa RadiskeMartín Cammarota
Dec 18, 2020·International Journal of Molecular Sciences·Genevieve Saw, Feng Ru Tang
Sep 15, 2020·European Journal of Pharmacology·Vignesh Balaji EMadhavan Nampoothiri

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