DNA methylation changes in plasticity genes accompany the formation and maintenance of memory
DNA methylation changes in plasticity genes accompany the formation and maintenance of memory
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DOI：
10.1038/nn.4194
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发表时间：
2016-01-01
影响因子：
25
通讯作者：
Bonn, Stefan
中科院分区：
文献类型：
--
作者：
Halder, Rashi;Hennion, Magali;Bonn, Stefan
形成记忆的能力是生物体对环境变化的行为适应的先决条件。在分子水平上，记忆的获得和维持需要染色质修饰的变化。为了解开短期和长期记忆背后的表观遗传网络，我们研究了两个不同的小鼠大脑区域，两种细胞类型和上下文学习前后三个时间点的染色质修饰变化。我们发现组蛋白修饰主要在记忆获得过程中发生变化，与基因表达的变化几乎没有相关性。虽然持久的变化几乎是神经元独有的，但学习相关的组蛋白修饰和DNA甲基化变化也发生在非神经元细胞类型中，这表明非神经元细胞在表观遗传学习中的功能作用。最后，我们的数据为记忆获得和维持的分子框架提供了证据，其中DNA甲基化可以改变参与功能可塑性和突触连接的基因的表达和剪接。
The ability to form memories is a prerequisite for an organism's behavioral adaptation to environmental changes. At the molecular level, the acquisition and maintenance of memory requires changes in chromatin modifications. In an effort to unravel the epigenetic network underlying both short- and long-term memory, we examined chromatin modification changes in two distinct mouse brain regions, two cell types and three time points before and after contextual learning. We found that histone modifications predominantly changed during memory acquisition and correlated surprisingly little with changes in gene expression. Although long-lasting changes were almost exclusive to neurons, learning-related histone modification and DNA methylation changes also occurred in non-neuronal cell types, suggesting a functional role for non-neuronal cells in epigenetic learning. Finally, our data provide evidence for a molecular framework of memory acquisition and maintenance, wherein DNA methylation could alter the expression and splicing of genes involved in functional plasticity and synaptic wiring.