Nuclear pore association confers optimal expression levels for an inducible yeast gene

The organization of the nucleus into subcompartments creates microenvironments that are thought to facilitate distinct nuclear functions(1). In budding yeast, regions of silent chromatin, such as those at telomeres and mating-type loci, cluster at the nuclear envelope creating zones that favour gene repression(1,2). Other reports indicate that gene transcription occurs at the nuclear periphery, apparently owing to association of the gene with nuclear pore complexes(3-5). Here we report that transcriptional activation of a subtelomeric gene, HXK1 ( hexokinase isoenzyme 1), by growth on a non-glucose carbon source led to its relocalization to nuclear pores. This relocation required the 30 untranslated region ( UTR), which is essential for efficient messenger RNA processing and export, consistent with an accompanying report(6). However, activation of HXK1 by an alternative pathway based on the transactivator VP16 moved the locus away from the nuclear periphery and abrogated the normal induction of HXK1 by galactose. Notably, when we interfered with HXK1 localization by either antagonizing or promoting association with the pore, transcript levels were reduced or enhanced, respectively. From this we conclude that nuclear position has an active role in determining optimal gene expression levels.