Abstract: In yeast, many genes are targeted to the nuclear periphery through interaction with the Nuclear Pore Complex upon activation. Targeting requires nucleoporin proteins and DNA elements in the promoters of these genes. We have recently found that targeting is regulated through the cell cycle. Immediately following the initiation of DNA replication, active genes lose peripheral localization for ~30 minutes. This regulation is mediated by cyclic phosphorylation of a nucleoporin by Cdk1. Some genes that are targeted to the nuclear periphery upon activation remain at the nuclear periphery after repression, a phenomenon called transcriptional memory. Curiously, the mechanism that regulates localization of active genes to the nuclear periphery does not regulate the localization of the same genes after repression, suggesting that these genes are targeted by two distinct mechanisms. Finally, the localization of other parts of the genome that localize at the nuclear periphery seem to be regulated by a distinct mechanism, suggesting that the spatial organization of the genome is tightly coupled to the progression of the cell cycle.