Epigenetics and epilepsy.
Epigenetics and epilepsy.
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作者：
Roopra A;Dingledine R;Hsieh J
癫痫发作可以引起持久的变化，这些变化反映了基因表达模式、细胞内和细胞间信号传导以及最终作为癫痫标志的网络改变的改变。越来越多的文献表明，与癫痫相关的基因转录的长期变化是通过调节染色质结构介导的。特别是一种转录因子REST（阻遏元件1-沉默转录因子），由于其可能控制驱动电路兴奋性、癫痫发作和癫痫的基本转录模式，因此受到了广泛关注。REST通过利用核蛋白复合物抑制神经系统中的一系列基因，这些核蛋白复合物最初被确定为表观遗传的介质。表观遗传学传统上指的是在没有DNA突变的情况下允许基因表达发生可遗传变化的机制。然而，一个更现代的定义承认，许多用于使分裂细胞中的表观遗传性状永久化的机制被神经元用来控制活性依赖性基因表达。这篇综述将调查目前所了解的表观遗传机制在癫痫中的作用。我们讨论了REST如何控制基因表达，以影响电路的兴奋性和癫痫的神经发生。我们还讨论了如何阻遏MeCP 2和激活CREB调节神经元的活动，并控制自己的活动。最后，我们强调了表观遗传学和癫痫领域未来可能的发展方向。
Seizures can give rise to enduring changes that reflect alterations in gene expression patterns, intra and inter cellular signaling and ultimately network alterations that are a hallmark of epilepsy. A growing body of literature suggests that long-term changes in gene transcription associated with epilepsy are mediated via modulation of chromatin structure. One transcription factor in particular, REST (repressor element 1-silencing transcription factor), has received a lot of attention due to the possibility that it may control fundamental transcription patterns that drive circuit excitability, seizures and epilepsy. REST represses a suite of genes in the nervous system by utilizing nuclear protein complexes that were originally identified as mediators of epigenetic inheritance. Epigenetics has traditionally referred to mechanisms that allow a heritable change in gene expression in the absence of DNA mutation. However a more contemporaneous definition acknowledges that many of the mechanisms used to perpetuate epigenetic traits in dividing cells are utilized by neurons to control activity dependent gene expression. This review will survey what is currently understood about the role of epigenetic mechanisms in epilepsy. We discuss how REST controls gene expression to effect circuit excitability and neurogenesis in epilepsy. We also discuss how the repressor MeCP2 and activator CREB regulate neuronal activity and are themselves controlled by activity. Finally we highlight possible future directions in the field of epigenetics and epilepsy.
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影响因子：
4.8
作者：
Abramovitz, Lilach;Shapira, Tamar;Vardimon, Lily
通讯作者：
Vardimon, Lily
DOI：
10.1073/pnas.96.17.9873
发表时间：
1999-08-17
影响因子：
11.1
作者：
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通讯作者：
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作者：
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通讯作者：
Mandel, G
DOI：
10.1073/pnas.0401827101
发表时间：
2004-07-13
影响因子：
11.1
作者：
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通讯作者：
Buckley, NJ
影响因子：
16.8
作者：
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通讯作者：
Cheng, Xiaodong