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DNA zip codes control an ancient mechanism for gene targeting to the nuclear periphery

Nature Cell Biology volume 12, pages 111–118 (2010)Cite this article

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A Corrigendum to this article was published on 01 March 2010

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Abstract

Many genes in Saccharomyces cerevisiae are recruited to the nuclear periphery after transcriptional activation. We have identified two gene recruitment sequences (GRS I and II) from the promoter of the INO1 gene that target the gene to the nuclear periphery. These GRSs function as DNA zip codes and are sufficient to target a nucleoplasmic locus to the nuclear periphery. Targeting requires components of the nuclear pore complex (NPC) and a GRS is sufficient to confer a physical interaction with the NPC. GRS I elements are enriched in promoters of genes that interact with the NPC, and genes that are induced by protein folding stress. Full transcriptional activation of INO1 and another GRS-containing gene requires GRS-mediated targeting of the promoter to the nuclear periphery. Finally, GRS I also functions as a DNA zip code in Schizosaccharomyces pombe, suggesting that this mechanism of targeting to the nuclear periphery has been conserved over approximately one billion years of evolution.

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Figure 1: Identification of a gene recruitment sequence (GRS) in the INO1 promoter.
Figure 2: Targeting of the endogenous INO1 gene is mediated by two redundant DNA zip codes.
Figure 3: GRS I mediated targeting to the nuclear periphery is general and ancient.
Figure 4: INO1 recruitment to the nuclear periphery requires components of the nuclear pore complex (NPC) and associated factors.
Figure 5: GRS I is enriched among genes that interact with many nuclear pore proteins.
Figure 6: Localization at the nuclear periphery enhances transcription of INO1.

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Change history

  • 27 January 2010

    In the version of this article initially published online, Fig. 4d was incorrectly labelled ‘Inositol’ instead of ‘GRS’. This error has been corrected in both the HTML and PDF versions of the article.

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Acknowledgements

We acknowledge Robert Lamb for generously sharing his confocal microscope. Also, we thank Audrey Gasch, Richard Carthew, Rick Gaber, Sandy Westerheide, Jonathan Widom, Susan Wente, Michael Rout and members of the Brickner lab for helpful discussions. This work was supported by the Searle Leadership Fund at Northwestern University, a gift of The Searle Funds at The Chicago Community Trust (J.H.B.), an Institutional Research Grant from the American Cancer Society (J.H.B.) and National Institutes of Health grant GM080484 (J.H.B.).

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  1. Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, 60208, IL, USA

    Sara Ahmed, Donna G. Brickner, William H. Light, Ivelisse Cajigas, Alexander B. Froyshteter & Jason H. Brickner

  2. Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, 60611, IL, USA

    Michele McDonough & Tom Volpe

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Contributions

S.A., D.G.B, T.V. and J.H.B designed the experiments, S.A., D.G.B., W.H.L., M.M., I.C., A.B.F. and J.H.B performed the experiments, S.A. and J.H.B wrote the manuscript.

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Correspondence to Jason H. Brickner.

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Ahmed, S., Brickner, D., Light, W. et al. DNA zip codes control an ancient mechanism for gene targeting to the nuclear periphery. Nat Cell Biol 12, 111–118 (2010). https://doi.org/10.1038/ncb2011

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