Yeast has been an excellent model for the conserved interaction between the nuclear pore complex (NPC) and hundreds of chromosomal loci. This interaction both affects transcriptional regulation and can lead to epigenetic transcriptional memory, poising inducible genes for faster reactivation for several generations after repression. I will discuss our work defining the molecular mechanisms that control gene positioning, interchromosomal clustering and transcriptional memory in association with the NPC. We find that localization at the nuclear periphery and interaction with the NPC is controlled by transcription factors and that this often leads to interallelic and intergenic clustering. A majority of transcription factors are capable of mediating targeting to the NPC by two major pathways, one that operates when genes are active and another that operates when they are poised. Poising results from the repurposing of factors associated with transcription (Mediator and COMPASS) to promote the poised state. Permissive chromatin changes lead to binding of RNA polymerase II preinitiation complex, bypassing the rate-limiting step in transcription.