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Cédrick Florian (CNRS/Université Paul Sabatier, Toulouse)

The transcriptional co-repressor Sin3A in memory formation

Long-term memory depends on the control of activity-dependent neuronal gene expression, which is regulated by epigenetic modifications. The epigenetic modification of histones is orchestrated by the opposing activities of two classes of regulatory complexes : permissive co-activators and silencing co-repressors. For example, histone acetylation, which is associated with transcriptional activation, increases at select learning-induced genes. Moreover pharmacological enhancement of histone acetylation with histone deacetylase (HDAC) inhibitors improves long-term memory formation. Much work has focused on co-activator complexes, but little is known about the co-repressor complexes that suppress the expression of plasticity-related genes. DNA methylation in gene regulatory elements is an epigenetic modification associated with transcriptional repression. Prior to learning, DNA-methylation recruits inhibitory complexes containing HDACs and the transcriptional co-repressor Sin3A to memory-promoting genes. Here, I will talk about the critical role for the co-repressor SIN3A in long-term memory formation and synaptic plasticity, and in age-related memory deficit in mice.