IQGAP1/ERK Regulates Fear Memory Formation via Histone Posttranslational Modifications Induced by HDAC2.

IQGAP1/ERK Regulates Fear Memory Formation via Histone Posttranslational Modifications Induced by HDAC2. Neurobiol Learn Mem. 2020 Mar 04;:107210 Authors: Liu XY, Yao B, Hao JR, Jin L, Gao Y, Yang X, Liu L, Sun XY, Sun N, Gao C Abstract Epigenetic mechanisms of learning and memory are particularly interesting topics in neuroscience that have recently been investigated. As shown in our previous study, IQGAP1, a scaffolding protein of MAPK, is involved in fear memory through interactions with GluN2A-containing NMDA receptors and the ERK1/2 cascade. However, researchers have not determined whether histone posttranslational modifications are regulated by the IQGAP1/ERK signaling pathway. We performed in vivo studies using IQGAP1-/- and IQGAP1+/+ mice to provide insights into the specific functions of IQGAP1 in memory processes and the precise mechanisms underlying its regulatory effects. IQGAP1-/- mice exhibited impaired fear memory, decreased levels of phosphorylated ERK1/2 and histone H3S10, decreased acetylation of H3K14, and decreased c-Fos expression in the hippocampus compared to IQGAP1+/+ mice after fear conditioning. HDAC2 was significantly enriched at the c-fos gene promoter in IQGAP1-/- mice. Correspondingly, the disruption of the epigenetic regulation induced by ERK1/2 signaling through an intra-hippocampal injection of the MEK antagonist U0126 or GluN2A-selective pharmacological antagonist NVP-AAM077 blocked context-dependent...
Source: Neurobiology of Learning and Memory - Category: Neurology Authors: Tags: Neurobiol Learn Mem Source Type: research