DNA 甲基化与建立记忆

IF 3.2 Q2 GENETICS & HEREDITY
Epigenetics Insights Pub Date : 2022-01-19 eCollection Date: 2022-01-01 DOI:10.1177/25168657211072499
Carol Bernstein
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引用次数: 0

摘要

一个事件可能会导致终身记忆。记忆实际上存在于神经元中,而神经元基因表达的变化被认为是记忆的核心。早期的模型提出,神经元 DNA 中胞嘧啶的特定 DNA 甲基化以稳定的生化形式编码记忆。本综述介绍了最近的研究,这些研究阐明了哺乳动物大脑形成 DNA 甲基胞嘧啶编码记忆的分子机制。例如,神经元激活通过刺激 DNA 拓扑异构酶 II beta(TOP2B)蛋白,在即刻早期基因 EGR1 的启动子上造成暂时的 DNA 双链断裂(约 2 小时内修复),使该基因得以表达,从而启动胞嘧啶去甲基化。然后,EGR1 蛋白招募甲基胞嘧啶二氧酶 TET1 蛋白,启动几百个基因的去甲基化,促进这些基因的表达。当 OGG1 定位于甲基化 CpG 位点的氧化鸟嘌呤并招募 TET1 启动该位点的去甲基化时,也会启动胞嘧啶的去甲基化。DNMT3A2 是另一种由突触活动上调的即时早期基因。DNMT3A2 蛋白可催化 DNA 的从头甲基化。这几种机制将外部经验转化为 DNA 甲基化,并启动神经元 DNA 胞嘧啶的去甲基化,从而引起基因表达的变化,这是长期记忆的基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

DNA Methylation and Establishing Memory.

DNA Methylation and Establishing Memory.

DNA Methylation and Establishing Memory.

DNA Methylation and Establishing Memory.

A single event can cause a life-long memory. Memories physically reside in neurons, and changes in neuronal gene expression are considered to be central to memory. Early models proposed that specific DNA methylations of cytosines in neuronal DNA encode memories in a stable biochemical form. This review describes recent research that elucidates the molecular mechanisms used by the mammalian brain to form DNA methylcytosine encoded memories. For example, neuron activation initiates cytosine demethylation by stimulating DNA topoisomerase II beta (TOP2B) protein to make a temporary DNA double-strand break (repaired within about 2 hours) at a promoter of an immediate early gene, EGR1, allowing expression of this gene. The EGR1 proteins then recruit methylcytosine dioxygenase TET1 proteins to initiate demethylation at several hundred genes, facilitating expression of those genes. Initiation of demethylation of cytosine also occurs when OGG1 localizes at oxidized guanine in a methylated CpG site and recruits TET1 for initiation of demethylation at that site. DNMT3A2 is another immediate early gene upregulated by synaptic activity. DNMT3A2 protein catalyzes de novo DNA methylations. These several mechanisms convert external experiences into DNA methylations and initiated demethylations of neuronal DNA cytosines, causing changes in gene expression that are the basis of long-term memories.

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来源期刊
Epigenetics Insights
Epigenetics Insights GENETICS & HEREDITY-
CiteScore
5.10
自引率
0.00%
发文量
10
审稿时长
8 weeks
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