Abstract
In addition to their role in regulating transport across the nuclear envelope, increasing evidence suggests nuclear pore complexes (NPCs) function in regulating gene expression. For example, the induction of certain genes (e.g., yeast INO1) is accompanied by their movement from the nuclear interior to NPCs. As sumoylation has been linked to the regulation of chromatin spatial organization and transcriptional activity, we investigated the role of sumoylation in the expression and NPC recruitment of the INO1 gene. We observed that induction of INO1 is accompanied by both increased and decreased sumoylation of proteins associated with specific regions along the INO1 locus. Furthermore, we show that the E3 ligase Siz2/Nfi1 is required for targeting the INO1 locus to the NPC where it interacts with the SUMO isopeptidase Ulp1. Our data suggest that this interaction is required for both the association of INO1 with the NPC and for its normal expression. These results imply that sumoylation is a key regulator of INO1 targeting to the NPC, and a cycle of sumoylation and NPC-associated desumoylation events contribute to the regulation of INO1 expression.
Highlights
Small ubiquitin-related modifier (SUMO) is an ubiquitin-like peptide that is covalently attached to certain lysines in proteins
We show that induction of INO1 is accompanied by Siz2-dependent sumoylation of proteins associated with the INO1 locus and propose that these modifications are required for targeting the gene to the nuclear pore complexes (NPCs)
Since changes in the expression of genes are often accompanied by changes in the levels of sumoylation of associated transcription factors (TFs) and other chromatin-associated proteins, we examined whether the induction of INO1 alters the sumoylation state of proteins associated with the INO1 locus
Summary
Small ubiquitin-related modifier (SUMO) is an ubiquitin-like peptide that is covalently attached to certain lysines in proteins. Alterations in sumoylation events have been shown to impact INO1 transcription (Felberbaum et al, 2012) Consistent with this idea, Ulp has been previously shown to contribute to the activation and NPC-binding of the GAL1 gene (Cabal et al, 2006; Texari et al, 2013). These observations and others implicating sumoylation in chromatin association with the NE and the regulation of gene expression has led us to investigate the role of sumoylation and desumoylation in the localization and expression of INO1. We propose that subsequent Ulp1-mediated desumoylation promotes expression and NPC association of activated INO1
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