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

Naturevolume 441pages774778 (2006) | Download Citation

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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 repression1,2. Other reports indicate that gene transcription occurs at the nuclear periphery, apparently owing to association of the gene with nuclear pore complexes3,4,5. 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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Acknowledgements

We thank T. Laroche, the imaging platform of the FMI, and the genomics platform of the NCCR for assistance, and E. Heard, A. Peters, G. Almouzni, D. Schübeler and M. Gartenberg for helpful suggestions, as well as G. Cabal and U. Nehrbass for sharing unpublished results. Our research is supported by the Swiss National Science Foundation, the NCCR programme ‘Frontiers in Genetics’, and the Novartis Research Foundation.

Author information

Affiliations

  1. Friedrich Miescher Institute for Biomedical Research, Basel, Maulbeerstrasse 66, CH-4058, Switzerland

    • Angela Taddei
    • , Florence Hediger
    • , Veronique Kalck
    • , Fabien Cubizolles
    • , Heiko Schober
    •  & Susan M. Gasser
  2. UMR 218, Centre National de la Recherche Scientifique/Institut Curie-Section de Recherche, 26 rue d'Ulm, 75231 Cedex 05, Paris, France

    • Angela Taddei
  3. University of Geneva, NCCR Frontiers in Genetics, Quai Ernest-Ansermet 30, CH-1211 4, Geneva, Switzerland

    • Griet Van Houwe
    • , Heiko Schober
    •  & Susan M. Gasser

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Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.

Corresponding author

Correspondence to Susan M. Gasser.

Supplementary information

  1. Supplementary Notes

    This file contains Supplementary Tables 1–3 and Supplementary Figure Legends. (DOC 70 kb)

  2. Supplementary Figure 1

    Abundance of the elongation-specific form of the RNA pol II on HXK1. (PDF 17 kb)

  3. Supplementary Figure 2

    HXK1 dynamics on glucose versus galactose media. (PDF 42 kb)

  4. Supplementary Figure 3

    Targeted VP16 allows variegated expression of subtelomeric ADE2 gene. (PDF 32 kb)

  5. Supplementary Figure 4

    VP16 targeting increases HXK1 dynamics. (PDF 35 kb)

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https://doi.org/10.1038/nature04845

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