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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 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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Figure 1: Relocation of HXK1 to the nuclear periphery on galactose requires the 3′ UTR.
Figure 2: HXK1 colocalizes with nuclear pores in glucose-free medium.
Figure 3: Alternative modes of transcriptional activation displace Tel6R from the nuclear periphery.
Figure 4: Impairing or improving perinuclear anchoring modulates HXK1 transcript levels on galactose.


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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G. Almouzni, D. Schübeler and M. Gartenberg for helpful suggestions, as well as G. Cabal and U. Nehrbass for sharing unpublished results.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.

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Correspondence to Susan M. Gasser.

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Supplementary information

Supplementary Notes

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

Supplementary Figure 1

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

Supplementary Figure 2

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

Supplementary Figure 3

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

Supplementary Figure 4

VP16 targeting increases HXK1 dynamics. (PDF 35 kb)

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Taddei, A., Van Houwe, G., Hediger, F. et al. Nuclear pore association confers optimal expression levels for an inducible yeast gene. Nature 441, 774–778 (2006).

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