The Nuclear Pore Regulates GAL1 Gene Transcription by Controlling the Localization of the SUMO Protease Ulp1

Transcription activation of some yeast genes correlates with their repositioning to the nuclear pore complex (NPC). The NPC-bound Mlp1 and Mlp2 proteins have been shown to associate with the GAL1 gene promoter and to maintain Ulp1, a key SUMO protease, at the NPC. Here, we show that the release of Ulp1 from the NPC increases the kinetics of GAL1 derepression, whereas artificial NPC anchoring of Ulp1 in the Δmlp1/2 strain restores normal GAL1 regulation. Moreover, artificial tethering of the Ulp1 catalytic domain to the GAL1 locus enhances the derepression kinetics. Our results also indicate that Ulp1 modulates the sumoylation state of Tup1 and Ssn6, two regulators of glucose-repressed genes, and that a loss of Ssn6 sumoylation correlates with an increase in GAL1 derepression kinetics. Altogether, our data highlight a role for the NPC-associated SUMO protease Ulp1 in regulating the sumoylation of gene-bound transcription regulators, positively affecting transcription kinetics in the context of the NPC. •Delocalization of Ulp1 from the NPC increases GAL1 derepression kinetics•Artificial NPC reanchoring of Ulp1 restores normal activation kinetics•Ulp1 delocalization decreases the sumoylation of the repressor Ssn6•Impairing Ssn6 sumoylation correlates with increased GAL1 activation kinetics