Laboratory of Transcription Dynamics, Research Center for Biological Visualization, Institute for Quantitative Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan.
Department of Bioinformatics and Systems Biology, Faculty of Science, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan.
Mol Cell. 2020 Apr 16;78(2):224-235.e5. doi: 10.1016/j.molcel.2020.02.007. Epub 2020 Feb 27.
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 developing Drosophila embryos. 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.
形成自我关联的环域是后生动物基因组的基本组织特征。在这里，我们采用定量活细胞成像方法来可视化高阶染色体拓扑结构对发育中的果蝇胚胎中增强子-启动子通讯的影响。有证据表明，当远端增强子被边界元件包围时，它们可以有效地从靶启动子远距离产生转录爆发。重要的是，边界元件的倒位或缺失都不会消除这种“增强子辅助活性”，这表明它们可以促进域内增强子-启动子相互作用和转录爆发的产生，而不依赖于拓扑关联域（TAD）的形成。相比之下，远端增强子的域跳跃活性在拓扑域被破坏后丧失。这一观察结果提出了一种可能性，即域内和域间增强子-启动子相互作用可能受到染色体拓扑结构的不同调节。
