| First Author | Liu XY | Year | 2020 |
| Journal | Neurobiol Learn Mem | Volume | 171 |
| Pages | 107210 | PubMed ID | 32145408 |
| Mgi Jnum | J:319504 | Mgi Id | MGI:6864358 |
| Doi | 10.1016/j.nlm.2020.107210 | Citation | Liu XY, et al. (2020) IQGAP1/ERK regulates fear memory formation via histone posttranslational modifications induced by HDAC2. Neurobiol Learn Mem 171:107210 |
| abstractText | 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 memory formation, while no changes were observed after treatment with the GluN2B-selective antagonist Ro25-6981. The administration of SAHA, a non-specific HDAC inhibitor, or knock-down of HDAC2 with shHDAC2-AAV in the dorsal hippocampus significantly rescued the impaired fear memory formation, H3S10 phosphorylation, H3K14 acetylation, and c-Fos expression in IQGAP1(-/-) mice. Thus, we postulated that the IQGAP1/ERK-dependent mechanism regulating histone posttranslational modifications via HDAC2 potentially underlies memory formation. |
