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转录增强子和染色体拓扑结构在基因调控中的动态变化。

Dynamics of transcriptional enhancers and chromosome topology in gene regulation.

机构信息

Institute for Quantitative Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.

Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.

出版信息

Dev Growth Differ. 2019 Jun;61(5):343-352. doi: 10.1111/dgd.12597. Epub 2019 Feb 19.

Abstract

Transcriptional enhancers are regulatory DNAs that instruct when and where genes should be transcribed in response to a variety of intrinsic and external signals. They contain a cluster of binding sites for sequence-specific transcription factors and co-activators to determine the spatiotemporal specificity of gene activities during development. Enhancers are often positioned in distal locations from their target promoters. In some cases, they work over a million base pairs or more. In the traditional view, enhancers have been thought to stably interact with promoters in a targeted manner. However, quantitative imaging studies provide a far more dynamic picture of enhancer action. Moreover, recent Hi-C methods suggest that regulatory interactions are dynamically regulated by the higher-order chromosome topology. In this review, we summarize the emerging findings in the field and propose that assembly of "transcription hubs" in the context of 3D genome structure plays an important role in transcriptional regulation.

摘要

转录增强子是调节 DNA,它们在接收到各种内在和外在信号时,会指示基因何时以及在何处转录。它们包含一组用于序列特异性转录因子和共激活因子的结合位点,以确定发育过程中基因活性的时空特异性。增强子通常位于其靶启动子的远端位置。在某些情况下,它们的作用距离可以超过一百万碱基。在传统观点中,增强子被认为以靶向方式与启动子稳定相互作用。然而,定量成像研究提供了一个更为动态的增强子作用图。此外,最近的 Hi-C 方法表明,调控相互作用受高级染色体拓扑结构的动态调节。在这篇综述中,我们总结了该领域的新发现,并提出在 3D 基因组结构背景下组装“转录枢纽”在转录调控中起着重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b771/6850047/06d3db9989db/DGD-61-343-g001.jpg

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