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染色质可及性和调控表观基因组。

Chromatin accessibility and the regulatory epigenome.

机构信息

Department of Genetics, Stanford University, Stanford, CA, USA.

Department of Applied Physics, Stanford University, Stanford, CA, USA.

出版信息

Nat Rev Genet. 2019 Apr;20(4):207-220. doi: 10.1038/s41576-018-0089-8.

Abstract

Physical access to DNA is a highly dynamic property of chromatin that plays an essential role in establishing and maintaining cellular identity. The organization of accessible chromatin across the genome reflects a network of permissible physical interactions through which enhancers, promoters, insulators and chromatin-binding factors cooperatively regulate gene expression. This landscape of accessibility changes dynamically in response to both external stimuli and developmental cues, and emerging evidence suggests that homeostatic maintenance of accessibility is itself dynamically regulated through a competitive interplay between chromatin-binding factors and nucleosomes. In this Review, we examine how the accessible genome is measured and explore the role of transcription factors in initiating accessibility remodelling; our goal is to illustrate how chromatin accessibility defines regulatory elements within the genome and how these epigenetic features are dynamically established to control gene expression.

摘要

DNA 的物理可接近性是染色质的一个高度动态特性,在建立和维持细胞身份方面发挥着至关重要的作用。基因组中可接近染色质的组织反映了一个允许的物理相互作用网络,通过这个网络,增强子、启动子、绝缘子和染色质结合因子协同调节基因表达。这种可及性景观会对外界刺激和发育线索做出动态响应,新出现的证据表明,可及性的动态维持本身是通过染色质结合因子和核小体之间的竞争相互作用来进行动态调节的。在这篇综述中,我们研究了如何测量可及基因组,并探讨了转录因子在启动可及性重塑中的作用;我们的目标是说明染色质可及性如何在基因组内定义调控元件,以及这些表观遗传特征是如何动态建立来控制基因表达的。

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