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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Theoretical analysis of the role of chromatin interactions in long-range action of enhancers and insulators
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Theoretical analysis of the role of chromatin interactions in long-range action of enhancers and insulators

机译：染色质相互作用在增强子和绝缘子远程作用中的作用的理论分析

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摘要

Long-distance regulatory interactions between enhancers and their target genes are commonplace in higher eukaryotes. Interposed boundaries or insulators are able to block these long-distance regulatory interactions. The mechanistic basis for insulator activity and how it relates to enhancer action-at-a-distance remains unclear. Here we explore the idea that topological loops could simultaneously account for regulatory interactions of distal enhancers and the insulating activity of boundary elements. We show that while loop formation is not in itself sufficient to explain action at a distance, incorporating transient nonspecific and moderate attractive interactions between the chromatin fibers strongly enhances long-distance regulatory interactions and is sufficient to generate a euchromatin-like state. Under these same conditions, the subdivision of the loop into two topologically independent loops by insulators inhibits interdomain interactions. The underlying cause of this effect is a suppression of crossings in the contact map at intermediate distances. Thus our model simultaneously accounts for regulatory interactions at a distance and the insulator activity of boundary elements. This unified model of the regulatory roles of chromatin loops makes several testable predictions that could be confronted with in vitro experiments, as well as genomic chromatin conformation capture and fluorescent microscopic approaches.
机译：增强子与其靶基因之间的远距离调控相互作用在高等真核生物中很普遍。插入的边界或绝缘体能够阻止这些长距离的调节相互作用。绝缘子活动的机制基础以及它与距离上的增强子作用之间的关系尚不清楚。在这里，我们探讨了拓扑回路可以同时说明远端增强子的调节相互作用和边界元素的绝缘活性的想法。我们显示，虽然环形成本身不足以解释某个距离的作用，但在染色质纤维之间掺入短暂的非特异性和中等吸引力的相互作用强烈增强了长距离调节相互作用，并足以产生类似常染色质的状态。在这些相同条件下，通过绝缘子将环路细分为两个拓扑独立的环路会抑制域间相互作用。造成这种影响的根本原因是抑制了接触图在中间距离处的交叉。因此，我们的模型同时考虑了远距离的调节相互作用和边界元素的绝缘子活性。染色质环调节作用的统一模型做出了一些可测试的预测，这些实验可能会与体外实验以及基因组染色质构象捕获和荧光显微镜方法面对。

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