1. Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland
2. UMR 218, Centre National de la Recherche Scientifique/Institut Curie-Section de Recherche, 26 rue d'Ulm, 75231 Paris Cedex 05, France
3. University of Geneva, NCCR Frontiers in Genetics, Quai Ernest-Ansermet 30, CH-1211 Geneva 4, Switzerland

Correspondence to: Susan M. Gasser^1,3 Correspondence and requests for materials should be addressed to S.G. (Email: susan.gasser@fmi.ch).

Abstract

The organization of the nucleus into subcompartments creates microenvironments that are thought to facilitate distinct nuclear functions¹. 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, 4, 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 3' untranslated region (UTR), which is essential for efficient messenger RNA processing and export, consistent with an accompanying report⁶. 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.

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