Visualizing the Role of Boundary Elements in Enhancer-Promoter Communication

Visualizing the Role of Boundary Elements in Enhancer-Promoter Communication
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可视化边界元素在增强子-启动子沟通中的作用

DOI:
10.1016/j.molcel.2020.02.007
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发表时间:
2020
期刊:
影响因子:
16
通讯作者:
Takashi Fukaya
Takashi Fukaya
中科院分区:
生物学1区
文献类型:
--
作者:
Moe Yokoshi;Kazuma Segawa;Takashi Fukaya

文献摘要

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自缔合环结构域的形成是后生动物基因组的基本组织特征。在这里,我们采用定量实时成像方法来可视化高阶染色体拓扑结构对果蝇胚胎发育中增强子-启动子通讯的影响。提供的证据表明,远端增强子有效地产生转录爆发从目标启动子的距离时,他们两侧的边界元素。重要的是,无论是倒位或删除的边界元件废除这种"增强子辅助活性",这表明它们可以促进域内增强子-启动子相互作用和生产的转录爆发独立的拓扑结构相关域(ESTA)的形成。相反,拓扑结构域破坏后,远端增强子的结构域跳跃活性丧失。这一观察结果提出了一种可能性,即域内和域间增强子-启动子相互作用受到染色体拓扑结构的差异调节。
Formation of self-associating loop domains is a fundamental organizational feature of metazoan genomes. Here, we employed quantitative live-imaging methods to visualize impacts of higher-order chromosome topology on enhancer-promoter communication in developingDrosophilaembryos. Evidence is provided that distal enhancers effectively produce transcriptional bursting from target promoters over distances when they are flanked with boundary elements. Importantly, neither inversion nor deletion of a boundary element abrogates this "enhancer-assisting activity," suggesting that they can facilitate intra-domain enhancer-promoter interaction and production of transcriptional bursting independently of topologically associating domain (TAD) formation. In contrast, domain-skipping activity of distal enhancers was lost after disruption of topological domains. This observation raises a possibility that intra-domain and inter-domain enhancer-promoter interactions are differentially regulated by chromosome topology.