Functional compartmentalization of the genome relies on interactions between genomic regions and various nuclear scaffolds and macro-complexes. The Nuclear Pore Complex (NPC) is a large nuclear envelope-embedded protein complex, which creates a highly regulated transport channel between the nucleus and the cytoplasm. In addition to its central role in transport, the NPC has been linked to genome compartmentalization via binding to specific regions of the genome and association with gene regulatory machinery. Although originally proposed to preferentially associate with active genes, the NPC has now been implicated in both gene activating and gene silencing processes. Here, we review recent findings that highlight the roles of various components of the NPC in transcriptional activation, transcriptional memory, heterochromatin formation, post-transcriptional gene silencing and RNA processing. Together, these findings suggest that the nuclear pore is utilized as a regulatory platform for a number of distinct gene expression processes and further point to its central role in setting up particular expression environments on the genomic template.