Core components of the nuclear pore bind distinct states of chromatin and contribute to Polycomb repression I

Interactions between the genome and the nuclear pore complex (NPC) have been implicated in multiple gene regulatory processes, but the underlying logic of these interactions remains poorly defined. Here, we report high-resolution chromatin binding maps of two core components of the NPC, Nup107 and Nup93, which reveal differential binding of these NPC subunits to active genes and Polycomb-covered silent regions, respectively. Comparison to Lamin-associated domains (LADs) revealed that NPC binding sites are often found within LADs, demonstrating a linear binding of the genome along the nuclear envelope. Significantly, we identified a functional role of Nup93 in silencing of Polycomb target genes and in spatial folding of Polycomb domains. Our findings lend to a model where nuclear pores bind different types of chromatin via interactions with specific core sub-complexes of the NPC, and the Nup93 sub-complex functions as a stabilizing scaffold for Polycomb domains. Overall design: Characterization of Elys, Nup93, and Nup107 by ChIP-Seq in Drosophila embryonic S2 cells.基因组与核孔复合体（NPC）的相互作用已被证实参与诸多基因调控进程，但此类相互作用的内在逻辑仍未得到清晰阐释。本研究报道了NPC的两类核心组分——核孔蛋白Nup107与Nup93的高分辨率染色质结合图谱，结果表明这两种NPC亚基分别与活跃基因及多梳蛋白覆盖的沉默区域存在差异性结合。通过与核纤层结合结构域（LADs）的比对分析发现，NPC结合位点常位于LADs内部，证实了基因组沿核被膜的线性结合模式。尤为关键的是，本研究鉴定出Nup93在沉默多梳蛋白靶基因以及调控多梳结构域空间折叠过程中的功能作用。本研究结果支持如下模型：核孔通过与NPC特定核心亚复合物的相互作用结合不同类型的染色质，而Nup93亚复合物可作为多梳结构域的稳定支架。整体实验设计：在果蝇胚胎S2细胞中，通过染色质免疫共沉淀测序（ChIP-Seq）对Elys、Nup93及Nup107进行表征。