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神经发育障碍中的表观遗传启动。

Epigenetic priming in neurodevelopmental disorders.

机构信息

Department of Neurology and Neurosurgery, Integrated Program in Neuroscience, McGill University, Montreal, QC, Canada.

Department of Neurology and Neurosurgery, Integrated Program in Neuroscience, McGill University, Montreal, QC, Canada.

出版信息

Trends Mol Med. 2021 Dec;27(12):1106-1114. doi: 10.1016/j.molmed.2021.09.005. Epub 2021 Oct 21.

Abstract

Neurodevelopmental disorders (NDDs) affect about 1% of the population and can be caused by mutations in genes that affect the epigenetic code. There is limited functional understanding of most of these epigenetic modifiers, and we suggest that associated NDDs are caused, in part, by deficits in epigenetic priming, a prepatterning step that alters the genome in preparation to make cells competent to signaling cues. We provide evidence from high-resolution epigenetic and transcriptomic mapping studies to demonstrate how a failure to adequately prime the genome for neural induction could lead to impairment of terminally differentiated cells. This idea provides a framework for NDD pathogenesis and treatment.

摘要

神经发育障碍 (NDDs) 影响约 1%的人口,可能是由影响表观遗传密码的基因突变引起的。大多数这些表观遗传修饰物的功能理解有限,我们认为,部分相关的 NDD 是由表观遗传启动缺陷引起的,这是一个预编程步骤,它改变基因组,为细胞准备好对信号提示做出反应。我们提供了来自高分辨率表观遗传和转录组图谱研究的证据,以证明基因组未能充分为神经诱导做好准备,可能导致终末分化细胞受损。这个想法为 NDD 的发病机制和治疗提供了一个框架。

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