Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

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

Subjects

A Corrigendum to this article was published on 01 March 2010

This article has been updated

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

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.

Similar content being viewed by others

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.

References

  1. Akhtar, A. & Gasser, S. M. The nuclear envelope and transcriptional control. Nature Rev. Genet. 8, 507–517 (2007).

    Article  CAS  PubMed  Google Scholar 

  2. Ahmed, S. & Brickner, J. H. Regulation and epigenetic control of transcription at the nuclear periphery. Trends Genet. 23, 396–402 (2007).

    Article  CAS  PubMed  Google Scholar 

  3. Taddei, A. Active genes at the nuclear pore complex. Curr. Opin. Cell Biol. 19, 305–310 (2007).

    Article  CAS  PubMed  Google Scholar 

  4. Casolari, J. M. et al. Genome-wide localization of the nuclear transport machinery couples transcriptional status and nuclear organization. Cell 117, 427–439 (2004).

    Article  CAS  PubMed  Google Scholar 

  5. Brickner, J. H. & Walter, P. Gene recruitment of the activated INO1 locus to the nuclear membrane. PLoS Biol. 2, e342 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Casolari, J. M., Brown, C. R., Drubin, D. A., Rando, O. J. & Silver, P. A. Developmentally induced changes in transcriptional program alter spatial organization across chromosomes. Genes Dev. 19, 1188–1198 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Dieppois, G., Iglesias, N. & Stutz, F. Cotranscriptional recruitment to the mRNA export receptor Mex67p contributes to nuclear pore anchoring of activated genes. Mol. Cell Biol. 26, 7858–7870 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  9. Sarma, N. J. et al. Glucose-responsive regulators of gene expression in Saccharomyces cerevisiae function at the nuclear periphery via a reverse recruitment mechanism. Genetics 175, 1127–1135 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Abruzzi, K. C., Belostotsky, D. A., Chekanova, J. A., Dower, K. & Rosbash, M. 3′-end formation signals modulate the association of genes with the nuclear periphery as well as mRNP dot formation. EMBO J. 25, 4253–4262 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Schmid, M. et al. Nup-PI: the nucleopore-promoter interaction of genes in yeast. Mol. Cell 21, 379–391 (2006).

    Article  CAS  PubMed  Google Scholar 

  12. Brickner, D. G. et al. H2A.Z-mediated localization of genes at the nuclear periphery confers epigenetic memory of previous transcriptional state. PLoS Biol. 5, e81 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  13. Straight, A. F., Belmont, A. S., Robinett, C. C. & Murray, A. W. GFP tagging of budding yeast chromosomes reveals that protein-protein interactions can mediate sister chromatid cohesion. Curr. Biol. 6, 1599–1608 (1996).

    Article  CAS  PubMed  Google Scholar 

  14. Robinett, C. C. et al. In vivo localization of DNA sequences and visualization of large-scale chromatin organization using lac operator/repressor recognition. J. Cell Biol. 135, 1685–1700 (1996).

    Article  CAS  PubMed  Google Scholar 

  15. Swift, S. & McGraw, P. INO1–100: an allele of the Saccharomyces cerevisiae INO1 gene that is transcribed without the action of the positive factors encoded by the INO2, INO4, SWI1, SWI2 and SWI3 genes. Nucleic Acids Res. 23, 1426–1433 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Harbison, C. T. et al. Transcriptional regulatory code of a eukaryotic genome. Nature 431, 99–104 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Lee, T. I. et al. Transcriptional regulatory networks in Saccharomyces cerevisiae. Science 298, 799–804 (2002).

    Article  CAS  PubMed  Google Scholar 

  18. Colman-Lerner, A., Chin, T. E. & Brent, R. Yeast Cbk1 and Mob2 activate daughter-specific genetic programs to induce asymmetric cell fates. Cell 107, 739–750 (2001).

    Article  CAS  PubMed  Google Scholar 

  19. Carmona-Saez, P., Chagoyen, M., Tirado, F., Carazo, J. M. & Pascual-Montano, A. GENECODIS: a web-based tool for finding significant concurrent annotations in gene lists. Genome Biol. 8, R3 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  20. Nogales-Cadenas, R. et al. GeneCodis: interpreting gene lists through enrichment analysis and integration of diverse biological information. Nucleic Acids Res. 37, W317–W322 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Cox, J. S., Chapman, R. E. & Walter, P. The unfolded protein response coordinates the production of endoplasmic reticulum protein and endoplasmic reticulum membrane. Mol. Biol. Cell 8, 1805–1814 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Gasch, A. P. et al. Genomic expression programs in the response of yeast cells to environmental changes. Mol. Biol. Cell 11, 4241–4257 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Travers, K. J. et al. Functional and genomic analyses reveal an essential coordination between the unfolded protein response and ER-associated degradation. Cell 101, 249–258 (2000).

    Article  CAS  PubMed  Google Scholar 

  24. Leber, J. H., Bernales, S. & Walter, P. IRE1-independent gain control of the unfolded protein response. PLoS Biol. 2, E235 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  25. Wong, C. M., Ching, Y. P., Zhou, Y., Kung, H. F. & Jin, D. Y. Transcriptional regulation of yeast peroxiredoxin gene TSA2 through Hap1p, Rox1p, and Hap2/3/5p. Free Radic. Biol. Med. 34, 585–597 (2003).

    Article  CAS  PubMed  Google Scholar 

  26. Heckman, D. S. et al. Molecular evidence for the early colonization of land by fungi and plants. Science 293, 1129–1133 (2001).

    Article  CAS  PubMed  Google Scholar 

  27. Luthra, R. et al. Actively transcribed GAL genes can be physically linked to the nuclear pore by the SAGA chromatin modifying complex. J. Biol. Chem. 282, 3042–3049 (2007).

    Article  CAS  PubMed  Google Scholar 

  28. Cabal, G. G. et al. SAGA interacting factors confine sub-diffusion of transcribed genes to the nuclear envelope. Nature 441, 770–773 (2006).

    Article  CAS  PubMed  Google Scholar 

  29. Menon, B. B. et al. Reverse recruitment: the Nup84 nuclear pore subcomplex mediates Rap1/Gcr1/Gcr2 transcriptional activation. Proc. Natl Acad. Sci. USA 102, 5749–5754 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Chekanova, J. A., Abruzzi, K. C., Rosbash, M. & Belostotsky, D. A. Sus1, Sac3, and Thp1 mediate post-transcriptional tethering of active genes to the nuclear rim as well as to non-nascent mRNP. RNA 14, 66–77 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Alber, F. et al. The molecular architecture of the nuclear pore complex. Nature 450, 695–701 (2007).

    Article  CAS  PubMed  Google Scholar 

  32. Sikorski, R. S. & Hieter, P. A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae. Genetics 122, 19–27 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Ghaemmaghami, S. et al. Global analysis of protein expression in yeast. Nature 425, 737–741 (2003).

    Article  CAS  PubMed  Google Scholar 

  34. Cox, J. S. & Walter, P. A novel mechanism for regulating activity of a transcription factor that controls the unfolded protein response. Cell 87, 391–404 (1996).

    Article  CAS  PubMed  Google Scholar 

  35. Longtine, M. S. et al. Additional modules for versatile and economical PCR-based gene deletion and modification in Saccharomyces cerevisiae. Yeast 14, 953–961 (1998).

    Article  CAS  PubMed  Google Scholar 

  36. Storici, F., Durham, C. L., Gordenin, D. A. & Resnick, M. A. Chromosomal site-specific double-strand breaks are efficiently targeted for repair by oligonucleotides in yeast. Proc. Natl Acad. Sci. USA 100, 14994–14999 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Grimm, C., Kohli, J., Murray, J. & Maundrell, K. Genetic engineering of Schizosaccharomyces pombe: a system for gene disruption and replacement using the ura4 gene as a selectable marker. Mol. Gen. Genet. 215, 81–86 (1988).

    Article  CAS  PubMed  Google Scholar 

  38. Miller, J. H. Experiments in Molecular Genetics. (Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 1972).

    Google Scholar 

Download references

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.).

Author information

Authors and Affiliations

  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

Authors
  1. Sara Ahmed
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Donna G. Brickner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. William H. Light
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ivelisse Cajigas
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michele McDonough
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Alexander B. Froyshteter
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tom Volpe
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jason H. Brickner
    View author publications

    You can also search for this author in PubMed Google Scholar

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.

Corresponding author

Correspondence to Jason H. Brickner.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Information

Supplementary Information (PDF 1334 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncb2011

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing