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Gene Repressive Mechanisms in the Mouse Brain Involved in Memory Formation
Nam-Kyung Yu1, Bong-Kiun Kaang1,*
1Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 151-747, Korea
Abstract
Gene regulation in the brain is essential for long-term plasticity and memory formation. Despite this established notion, the quantitative translational map in the brain during memory formation has not been reported. Therefore, our recent study exploited ribosome profiling using the mouse hippocampal tissues at multiple time points after a learning event. Analysis of the resulting database found novel types of gene regulation after learning. First, the translation of a group of genes was rapidly suppressed without any change in mRNA levels. At later time points, expression of another group of genes was downregulated through reduction in mRNA levels. This reduction was predicted to be downstream of inhibition of ESR1 (Estrogen Receptor 1) signaling. Overexpressing Nrsn1, one of the genes whose translation was suppressed, or activating ESR1 by injecting an agonist interfered with memory formation, suggesting the functional importance of these findings. Moreover, the translation of genes encoding the translational machineries was found to be suppressed, among other genes in the mouse hippocampus. Together, this unbiased approach has revealed previously unidentified characteristics of gene regulation in the brain and highlighted the importance of repressive controls.
Abstract, Accepted Manuscript [Submitted on March 3, 2016, Accepted on March 4, 2016]
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