Metazoan Nuclear Pores Provide a Scaffold for Poised Genes and Mediate Induced Enhancer-Promoter Contacts.
Metazoan Nuclear Pores Provide a Scaffold for Poised Genes and Mediate Induced Enhancer-Promoter Contacts.
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DOI：
10.1016/j.molcel.2017.02.020
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发表时间：
2017-04-06
期刊：
影响因子：
16
通讯作者：
Capelson M
中科院分区：
文献类型：
--
作者：
Pascual-Garcia P;Debo B;Aleman JR;Talamas JA;Lan Y;Nguyen NH;Won KJ;Capelson M
核孔复合体成分（Nups）与转录调控有关，但后生动物 Nups 控制哪些调控步骤仍不清楚。我们在果蝇基因组中的启动子、增强子和绝缘子上发现了多个 Nups 的存在。与这种结合一致，我们发现了 Nup98 在介导蜕皮激素诱导基因的增强子-启动子环中的功能作用。发现这些基因在激活前后与核孔稳定相关。尽管 Nup98 水平的变化破坏了增强子-启动子的接触，但它并没有影响正在进行的转录，而是损害了随后的转录激活或转录记忆。为了支持增强子循环作用，我们发现 Nup98 在受到蜕皮激素刺激后能够获得并保留与结构蛋白的物理相互作用。总之，我们的数据将 Nups 确定为一类增强子的结构蛋白，并支持动物基因组使用核孔作为可诱导平衡基因的组织支架的模型。已知核孔成分 (Nups) 与染色质相互作用，但 Nups 在基因调控中的精确机制作用仍未完全确定。现在，帕斯夸尔-加西亚等人的发现。揭示沉默基因可以通过核孔结合，在激活时促进增强子-启动子循环。
Nuclear pore complex components (Nups) have been implicated in transcriptional regulation, yet what regulatory steps are controlled by metazoan Nups remains unclear. We identified the presence of multiple Nups at promoters, enhancers, and insulators in the Drosophila genome. In line with this binding, we uncovered a functional role for Nup98 in mediating enhancer-promoter looping at ecdysone-inducible genes. These genes were found to be stably associated with nuclear pores before and after activation. Although changing levels of Nup98 disrupted enhancer-promoter contacts, it did not affect ongoing transcription but instead compromised subsequent transcriptional activation or transcriptional memory. In support of the enhancer-looping role, we found Nup98 to gain and retain physical interactions with architectural proteins upon stimulation with ecdysone. Together, our data identify Nups as a class of architectural proteins for enhancers and supports a model in which animal genomes use the nuclear pore as an organizing scaffold for inducible poised genes. Nuclear pore components (Nups) are known to interact with chromatin, but the precise mechanistic roles of Nups in gene regulation remain incompletely defined. Now, findings from Pascual-Garcia et al. reveal that silent genes can be bound by nuclear pores to promote enhancer-promoter looping upon activation.
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