Covalent modification of DNA regulates memory formation
Covalent modification of DNA regulates memory formation
复制标题
DOI：
10.1016/j.neuron.2007.02.022
复制
发表时间：
2007-03-15
期刊：
影响因子：
16.2
通讯作者：
Sweatt, J. David
中科院分区：
文献类型：
--
作者：
Miller, Courtney A.;Sweatt, J. David
DNA甲基化是由DNA甲基转移酶（dnmt）催化的DNA共价化学修饰。DNA甲基化与转录沉默有关，作为一种终身的分子信息存储机制，在发育过程中得到了广泛的研究。在这里，我们报道了DNMT基因表达上调在成年大鼠海马后情境恐惧条件反射和DNMT抑制阻止记忆形成。此外，恐惧条件作用与记忆抑制基因PP1的快速甲基化和转录沉默以及突触可塑性基因reelin的去甲基化和转录激活有关，表明在巩固过程中甲基转移酶和去甲基化酶都具有活性。DNMT抑制阻止PP1甲基化增加，导致该基因在记忆巩固期间的异常转录。这些结果表明，DNA甲基化在成人神经系统中是动态调节的，这种细胞机制是记忆形成的关键步骤。
DNA methylation is a covalent chemical modification of DNA catalyzed by DNA methyltransferases (DNMTs). DNA methylation is associated with transcriptional silencing and has been studied extensively as a lifelong molecular information storage mechanism put in place during development. Here we report that DNMT gene expression is upregulated in the adult rat hippocampus following contextual fear conditioning and that DNMT inhibition blocks memory formation. In addition, fear conditioning is associated with rapid methylation and transcriptional silencing of the memory suppressor gene PP1 and demethylation and transcriptional activation of the synaptic plasticity gene reelin, indicating both methyltransferase and demethylase activity during consolidation. DNMT inhibition prevents the PP1 methylation increase, resulting in aberrant transcription of the gene during the memory-consolidation period. These results demonstrate that DNA methylation is dynamically regulated in the adult nervous system and that this cellular mechanism is a crucial step in memory formation.