Nuclear genome architecture relies on interactions between the genome and various nuclear scaffolds. One such a nuclear scaffold is the nuclear pore complex (NPC), which in addition to its nuclear transport function, can interact with underlying chromatin. In particular, NPCs have been recently reported to associate with a number of enhancers and superenhancers in metazoan genomes, and select NPC components have been shown to promote the formation of specific genomic loops. Here, we provide a brief overview of current models of enhancer function, and discuss recent evidence that NPCs bind enhancers and contribute to topological genome organization. We also examine possible models of how gene and enhancer targeting to NPCs may contribute to tissue-specific genome architecture and expression programs, including the possibility that NPCs may promote phase separation of transcriptional compartments.
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