Ultra-long-range interactions between active regulatory elements.
Ultra-long-range interactions between active regulatory elements.
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DOI：
10.1101/gr.277567.122
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发表时间：
2023-08
期刊：
影响因子：
7
通讯作者：
Bickmore, Wendy A
中科院分区：
文献类型：
--
作者：
Friman, Elias T;Flyamer, Ilya M;Marenduzzo, Davide;Boyle, Shelagh;Bickmore, Wendy A
增强子和启动子之间的接触被认为与它们激活转录的能力有关。因此，研究有助于这种染色质相互作用的因素对于理解基因调控是重要的。在这里，我们已经确定了数以百万计的顺式调控元件对染色体构象捕获数据集之间的接触频率，并分析了数百个DNA结合因子的集合，用于在富集接触区域的结合。该分析揭示了与活跃转录相关的许多因子结合的位点处的富集接触。我们发现，活跃的调控元件，独立的凝聚素和polycomb，相互作用跨越数十兆碱基的距离在脊椎动物和无脊椎动物的基因组和相互作用的相关性和变化与活动。然而，这些超远程相互作用不依赖于RNA聚合酶II转录或单个转录辅因子。使用模拟，我们表明，染色质和多价结合因子的模型可以引起远程相互作用，通过桥接诱导聚类。我们提出，顺式调控元件之间的长程相互作用是由至少三个不同的过程驱动：粘附素介导的环挤出，polycomb接触，和集群的活性区域。
Contacts between enhancers and promoters are thought to relate to their ability to activate transcription. Investigating factors that contribute to such chromatin interactions is therefore important for understanding gene regulation. Here, we have determined contact frequencies between millions of pairs of cis-regulatory elements from chromosome conformation capture data sets and analyzed a collection of hundreds of DNA-binding factors for binding at regions of enriched contacts. This analysis revealed enriched contacts at sites bound by many factors associated with active transcription. We show that active regulatory elements, independent of cohesin and polycomb, interact with each other across distances of tens of megabases in vertebrate and invertebrate genomes and that interactions correlate and change with activity. However, these ultra-long-range interactions are not dependent on RNA polymerase II transcription or individual transcription cofactors. Using simulations, we show that a model of chromatin and multivalent binding factors can give rise to long-range interactions via bridging-induced clustering. We propose that long-range interactions between cis-regulatory elements are driven by at least three distinct processes: cohesin-mediated loop extrusion, polycomb contacts, and clustering of active regions.