Sumoylation and transcription regulation at nuclear pores

Abstract

Increasing evidence indicates that besides promoters, enhancers, and epigenetic modifications, nuclear organization is another parameter contributing to optimal control of gene expression. Although differences between species exist, the influence of gene positioning on expression seems to be a conserved feature from yeast to Drosophila and mammals. The nuclear periphery is one of the nuclear compartments implicated in gene regulation. It consists of the nuclear envelope (NE) and the nuclear pore complexes (NPC), which have distinct roles in the control of gene expression. The NPC has recently been shown to tether proteins involved in the sumoylation pathway. Here, we will focus on the importance of gene positioning and NPC-linked sumoylation/desumoylation in transcription regulation. We will mainly discuss observations made in the yeast Saccharomyces cerevisiae model system and highlight potential parallels in metazoan species.

Fig. 1

Gene to pore interactions in yeast are mediated by factors involved in transcription and mRNA biogenesis as well as NPC basket-associated proteins (left). The composition of the main yeast complexes involved in this process is indicated in the box below the drawing.f The SUMO protease Ulp1 and its mammalian counterparts SENP1 and SENP2 interact with homologous NPC components (right). While genes move to pores in yeast, nucleoporins are dynamic in metazoans and interact with target genes in the nucleoplasm. The factors conserved between yeast and metazoans are drawn with the same color code. See text for more details and references

Fig. 2

A speculative model is that the yeast NPC-associated SUMO protease Ulp1 (left) may desumoylate many target proteins involved in chromatin organization and transcription when active genes relocate to the pore, but also factors involved in DNA repair (not shown). In metazoans (right), SENP1 and SENP2 may move away from the NPC in association with dynamic pore components and desumoylate their specific targets within the nucleoplasm. The factors conserved between yeast and metazoans are drawn with the same color code