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中枢神经系统中的组蛋白调控:表观遗传可塑性的基本原则。

Histone regulation in the CNS: basic principles of epigenetic plasticity.

机构信息

Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New York, NY 10065, USA.

出版信息

Neuropsychopharmacology. 2013 Jan;38(1):3-22. doi: 10.1038/npp.2012.124. Epub 2012 Jul 25.

Abstract

Postmitotic neurons are subject to a vast array of environmental influences that require the nuclear integration of intracellular signaling events to promote a wide variety of neuroplastic states associated with synaptic function, circuit formation, and behavioral memory. Over the last decade, much attention has been paid to the roles of transcription and chromatin regulation in guiding fundamental aspects of neuronal function. A great deal of this work has centered on neurodevelopmental and adulthood plasticity, with increased focus in the areas of neuropharmacology and molecular psychiatry. Here, we attempt to provide a broad overview of chromatin regulation, as it relates to central nervous system (CNS) function, with specific emphasis on the modes of histone posttranslational modifications, chromatin remodeling, and histone variant exchange. Understanding the functions of chromatin in the context of the CNS will aid in the future development of pharmacological therapeutics aimed at alleviating devastating neurological disorders.

摘要

有丝分裂后的神经元会受到大量环境影响,这些影响需要将细胞内信号事件整合到核内,以促进与突触功能、回路形成和行为记忆相关的多种神经可塑性状态。在过去的十年中,人们对转录和染色质调节在指导神经元功能基本方面的作用给予了极大关注。这项工作很大程度上集中在神经发育和成年期的可塑性上,神经药理学和分子精神病学领域的关注度也有所增加。在这里,我们试图提供一个与中枢神经系统(CNS)功能相关的染色质调节的广泛概述,特别强调组蛋白翻译后修饰、染色质重塑和组蛋白变体交换的模式。在 CNS 背景下理解染色质的功能将有助于未来开发旨在缓解毁灭性神经疾病的药理学治疗方法。

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