Genomic insights into MeCP2 function: A role for the maintenance of chromatin architecture
Genomic insights into MeCP2 function: A role for the maintenance of chromatin architecture
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DOI：
10.1016/j.conb.2019.07.002
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发表时间：
2019-12-01
影响因子：
5.7
通讯作者：
Zhou, Zhaolan
中科院分区：
文献类型：
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作者：
Connolly, Daniel R.;Zhou, Zhaolan
甲基 CpG 结合蛋白 2 (MeCP2) 在神经系统中发挥着重要作用，因为 MECP2 的功能获得和功能丧失都与严重的神经系统疾病相关。了解 MeCP2 的分子功能不仅可以深入了解 MeCP2 相关疾病的发病机制，还可以揭示神经元功能的表观遗传调控。在过去的几年中，许多研究提供了 MeCP2 将共阻遏物复合物招募到特定甲基化 DNA 序列的机制证据。此外，创新设计和高通量测序技术为研究 MeCP2 对神经元转录组的影响提供了前所未有的详细程度，证明 MeCP2 以特定环境的方式调节基因表达。这些发现提出了新的问题并对当前的 MeCP2 功能模型提出了挑战。在这篇综述中，我们描述了最近的一些进展，强调了未来的挑战，并阐明了一个模型，通过该模型，MeCP2 作为染色质结构的组织者来调节神经系统中的全局基因表达。
Methyl-CpG binding protein 2 (MeCP2) plays fundamental roles in the nervous system, as both gain-of-function and loss-offunction of MECP2 are associated with severe neurological conditions. Understanding the molecular function of MeCP2 will not only provide insights into the pathogenesis of MeCP2-related disorders, but will also shed light on the epigenetic regulation of neuronal function. In the past few years, a number of studies have provided mechanistic evidence that MeCP2 recruits co-repressor complexes to particular sequences of methylated DNA. Additionally, innovative design and high-throughput sequencing technologies have provided opportunities to study the effects of MeCP2 on the neuronal transcriptome at an unprecedented level of detail, demonstrating that MeCP2 modulates gene expression in a context-specific manner. These findings have raised new questions and challenged current models of MeCP2 function. In this review, we describe several recent developments, highlight future challenges, and articulate a model by which MeCP2 functions as an organizer of chromatin architecture to modulate global gene expression in the nervous system.