Quintero-Cadena Porfirio, Sternberg Paul W
Division of Biology and Biological Engineering, California Institute of Technology, Howard Hughes Medical Institute, Pasadena, California 91125.
Division of Biology and Biological Engineering, California Institute of Technology, Howard Hughes Medical Institute, Pasadena, California 91125
G3 (Bethesda). 2016 Dec 7;6(12):4167-4174. doi: 10.1534/g3.116.036228.
Enhancers physically interact with transcriptional promoters, looping over distances that can span multiple regulatory elements. Given that enhancer-promoter (EP) interactions generally occur via common protein complexes, it is unclear whether EP pairing is predominantly deterministic or proximity guided. Here, we present cross-organismic evidence suggesting that most EP pairs are compatible, largely determined by physical proximity rather than specific interactions. By reanalyzing transcriptome datasets, we find that the transcription of gene neighbors is correlated over distances that scale with genome size. We experimentally show that nonspecific EP interactions can explain such correlation, and that EP distance acts as a scaling factor for the transcriptional influence of an enhancer. We propose that enhancer sharing is commonplace among eukaryotes, and that EP distance is an important layer of information in gene regulation.
增强子与转录启动子发生物理相互作用，在跨越多个调控元件的距离上形成环状结构。鉴于增强子 - 启动子（EP）相互作用通常通过常见的蛋白质复合物发生，目前尚不清楚EP配对主要是由确定性因素还是邻近性引导的。在这里，我们提供了跨生物的证据，表明大多数EP对是兼容的，很大程度上由物理邻近性而非特定相互作用决定。通过重新分析转录组数据集，我们发现基因邻域的转录在与基因组大小成比例的距离上具有相关性。我们通过实验表明，非特异性的EP相互作用可以解释这种相关性，并且EP距离作为增强子转录影响的缩放因子。我们提出增强子共享在真核生物中很常见，并且EP距离是基因调控中重要的信息层。
