The histone H3 lysine 9 methyltransferase G9a/GLP complex activity is required for long-term consolidation of spatial memory in mice

The G9a/G9a-like protein (GLP) histone lysine dimethyltransferase complex and downstream H3 9 dimethylation (H3K9me2) repressive mark have recently emerged as key transcriptional regulators of gene expression programs necessary for long-term memory (LTM) formation in the dorsal hippocampus. However, role hippocampal G9a/GLP mediating consolidation spatial LTM remains largely unknown. Using a water maze competition task which both hippocampus-dependent striatum-dependent cue navigation strategies are effective to solve maze, we found that pharmacological inhibition activity immediately after learning disrupts previously learned information male mice, hence producing bias on test performed 24 h later. Importantly, did not disrupt short-term retention. Immunohistochemical analyses revealed increases global levels permissive H3K9 acetylation hippocampus striatum at 1 post-training, persisted up Conversely, H3K9me2 were either unchanged or transiently decreased 15 min post-training striatum. Finally, further increased while decreasing post-training. marks returned vehicle control h. Together, these findings support possibility is required switch from formation.