生物
表观遗传学
DNA甲基化
记忆巩固
甲基转移酶
海马体
细胞生物学
长期记忆
神经科学
甲基化
遗传学
基因表达
基因
认知
作者
Janina Kupke,Julien Klimmt,Franziska Mudlaff,Maximilian Schwab,Carsten Sticht,Ana M.M. Oliveira
标识
DOI:10.1101/2023.05.22.541739
摘要
Abstract Epigenetic factors are well established players in memory formation. Specifically, DNA methylation is necessary for the formation of long-term memory in multiple brain regions including the hippocampus. Despite the demonstrated role for DNA methyltransferases (Dnmts) in memory formation, it is unclear whether individual Dnmts have unique or redundant functions in long-term memory formation. Furthermore, the downstream processes controlled by Dnmts during memory consolidation have not been investigated. In this study, we examined the requirement of the predominant Dnmt in the adult brain, Dnmt3a1, for hippocampus- dependent long-term memory formation. Using RNA-sequencing, we identified an activity- regulated Dnmt3a1-dependent genomic program in which several genes were functionally associated with functional and structural plasticity. Our data showed that Dnmt3a1, similarly to its isoform Dnmt3a2, plays a critical role in memory formation and identified Neuropilin 1 (Nrp1) as a downstream target of Dnmt3a1 in this process. Intriguingly, we found that Nrp1 expression is selectively regulated by and a specific downstream effector of Dnmt3a1, but not Dnmt3a2. Taken together, our study uncovered a Dnmt3a-isoform-specific mechanism in memory formation, identified a novel regulator of memory, and further highlighted the complex and highly regulated functions of distinct epigenetic regulators in brain function.
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