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Telomere looping permits gene activation by a downstream UAS in yeast

Nature volume 409, pages 109–113 (2001)Cite this article

Abstract

In yeast (Saccharomyces cerevisiae), transcriptional activators, such as Gal4 and Gal4–VP16, work ordinarily from sites located in the upstream activating sequence (UAS) positioned about 250 base pairs upstream of the transcription start site1. In contrast to their behaviour in mammalian cells, however, such activators fail to work when positioned at distances greater than ∼600–700 base pairs upstream2, or anywhere downstream3,4 of the gene. Here we show that, in yeast, a gene bearing an enhancer positioned 1–2 kilobases downstream of the gene is activated if the reporter is linked to a telomere, but not if it is positioned at an internal chromosomal locus. These observations are explained by the finding that yeast telomeres form back-folding, or looped, structures. Because yeast telomeric regions resemble the heterochromatin found in higher eukaryotes, these findings might also explain why transcription of some higher eukaryotic genes depends on their location in heterochromatin.

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Figure 1: Telomere-linked reporter gene constructs and model of gene activation.
Figure 2: Overcoming TPE by an activator working from the downstream direction.
Figure 3: Dependence on telomere linkage for downstream activation.
Figure 4: SIR3-dependent downstream activation of a telomere-linked gene as assayed by mRNA levels.
Figure 5: Telomere looping as assayed by chromosomal immunopercipitation (ChIP).

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Acknowledgements

We wish to thank S. Kantrow for her technical assistance and G. Bryant for his help with the quantitative PCR analysis. We are grateful to J. V. Ravetch, Head, Laboratory of Molecular Genetics & Immunology, The Rockefeller University, for his support of D.d.B. and R.A.L. during this work. We also thank T. De Lange and M. Grunstein for comments on the manuscript. M.P. is a Ludwig Foundation Professor. This work was supported in part by NIH and a fellowship from the Norman and Rosita Winston Foundation (Z.Z.).

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Authors and Affiliations

  1. The Rockefeller University, Laboratory of Molecular Genetics & Immunology, 1230 York Avenue, New York, 10021, New York, USA

    Derik de Bruin & Rachel A. Liberatore

  2. Molecular Biology Program, Sloan-Kettering Institute for Cancer Research, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, 10021, New York, USA

    Zafar Zaman & Mark Ptashne

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  1. Derik de Bruin
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Correspondence to Derik de Bruin.

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de Bruin, D., Zaman, Z., Liberatore, R. et al. Telomere looping permits gene activation by a downstream UAS in yeast. Nature 409, 109–113 (2001). https://doi.org/10.1038/35051119

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