Pascual-Garcia Pau, Debo Brian, Aleman Jennifer R, Talamas Jessica A, Lan Yemin, Nguyen Nha H, Won Kyoung J, Capelson Maya
Department of Cell and Developmental Biology, Epigenetics Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Mol Cell. 2017 Apr 6;66(1):63-76.e6. doi: 10.1016/j.molcel.2017.02.020. Epub 2017 Mar 30.
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.
核孔复合体成分（核孔蛋白）已被证明与转录调控有关，但后生动物核孔蛋白控制哪些调控步骤仍不清楚。我们在果蝇基因组的启动子、增强子和绝缘子处发现了多种核孔蛋白的存在。与这种结合一致，我们发现核孔蛋白98（Nup98）在介导蜕皮激素诱导基因的增强子-启动子环化中发挥功能作用。这些基因在激活前后都与核孔稳定相关。虽然Nup98水平的变化破坏了增强子-启动子的接触，但它并不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。为支持增强子环化作用，我们发现Nup98在蜕皮激素刺激后与结构蛋白获得并保持物理相互作用。总之，我们的数据将核孔蛋白鉴定为一类增强子的结构蛋白，并支持一种模型，即动物基因组利用核孔作为可诱导的就绪基因的组织支架。
