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解析染色质结构,深入了解大脑疾病的病因。

Disentangling chromatin architecture to gain insights into the etiology of brain disorders.

机构信息

Department of Genetics and Epigenetics Institute, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.

Department of Genetics and Epigenetics Institute, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.

出版信息

Curr Opin Genet Dev. 2019 Apr;55:76-81. doi: 10.1016/j.gde.2019.06.009. Epub 2019 Jul 16.

Abstract

Chromatin organization, together with DNA and histone modifications, is directly linked to the spatiotemporal control of gene expression that specifies and maintains cell type-specific functions. This is particularly important in the brain where hundreds of cell types with distinct functions reside. Recent advances in molecular and computational technologies have enabled the query of chromatin architecture at unprecedented resolution and detail. Here, we review recent studies on the emerging importance of chromatin architecture in the pathogenesis of brain disorders, with emphasis on schizophrenia, autism spectrum disorders (ASD), and unstable repeat expansion disorders. These studies provide molecular insights into how these brain disorders arise at the level of chromatin architecture and implicate new therapeutic directions.

摘要

染色质组织与 DNA 和组蛋白修饰直接相关,它控制着基因表达的时空调控,从而决定并维持着细胞类型特异性的功能。在大脑中,数百种具有不同功能的细胞类型存在,这一点尤为重要。分子和计算技术的最新进展使人们能够以前所未有的分辨率和细节来研究染色质结构。在这里,我们回顾了最近关于染色质结构在脑疾病发病机制中的重要性的研究,重点是精神分裂症、自闭症谱系障碍 (ASD) 和不稳定重复扩展障碍。这些研究提供了分子层面上的见解,说明了这些脑疾病是如何在染色质结构层面上产生的,并提出了新的治疗方向。

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