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Regulatory Landscaping: How Enhancer-Promoter Communication Is Sculpted in 3D.
Molecular Cell ( IF 14.5 ) Pub Date : 2019-06-20 , DOI: 10.1016/j.molcel.2019.05.032
Michael I Robson 1 , Alessa R Ringel 1 , Stefan Mundlos 2
Affiliation  

During embryogenesis, precise gene transcription in space and time requires that distal enhancers and promoters communicate by physical proximity within gene regulatory landscapes. To achieve this, regulatory landscapes fold in nuclear space, creating complex 3D structures that influence enhancer-promoter communication and gene expression and that, when disrupted, can cause disease. Here, we provide an overview of how enhancers and promoters construct regulatory landscapes and how multiple scales of 3D chromatin structure sculpt their communication. We focus on emerging views of what enhancer-promoter contacts and chromatin domains physically represent and how two antagonistic fundamental forces-loop extrusion and homotypic attraction-likely form them. We also examine how these same forces spatially separate regulatory landscapes by functional state, thereby creating higher-order compartments that reconfigure during development to enable proper enhancer-promoter communication.

中文翻译:

监管环境美化:如何以 3D 形式塑造增强剂-促进剂通信。

在胚胎发生过程中,空间和时间上的精确基因转录需要远端增强子和启动子通过基因调控景观内的物理接近进行通信。为了实现这一点,核空间中的监管环境折叠起来,创造出复杂的 3D 结构,这些结构影响增强子-启动子的交流和基因表达,一旦被破坏,就会导致疾病。在这里,我们概述了增强子和启动子如何构建监管景观,以及多尺度 3D 染色质结构如何塑造它们的交流。我们专注于增强子-启动子接触和染色质结构域物理代表的新兴观点,以及两种对立的基本力——环挤压和同型吸引力——如何形成它们。
更新日期:2019-06-20
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