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Telomere length regulates TERRA levels through increased trimethylation of telomeric H3K9 and HP1α

An Erratum to this article was published on 05 February 2013

This article has been updated

Abstract

Gene silencing by the repressive telomeric chromatin environment, referred to as telomere position effect (TPE), has been well characterized in yeast and depends on telomere length. However, proof of its existence at native human chromosome ends has remained elusive, mainly owing to the paucity of genes near telomeres. The discovery of TERRAs, the telomeric noncoding RNAs transcribed from subtelomeric promoters, paved the way to probing for telomere-length impact on physiological TPE. Using cell lines of various origins, we show that telomere elongation consistently represses TERRA expression. Repression is mediated by increased trimethylated H3K9 density at telomeres and by heterochromatin protein HP1α, with no detectable spreading of the marks beyond the telomeric tract, restricting human TPE to telomere transcription. Our data further support the existence of a negative-feedback mechanism in which longer TERRA molecules repress their own transcription upon telomere elongation.

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Figure 1: Telomere elongation decreases TERRA molecule levels.
Figure 2: Telomere length negatively regulates TERRA expression.
Figure 3: H3K9me3 density is higher at elongated telomeres.
Figure 4: HP1α and H3K9me3 are involved in telomere length–dependent repression of TERRAs.
Figure 5: Telomere elongation increases UUAGGG levels at telomeres.
Figure 6: TERRA length increases in cells with elongated telomeres.
Figure 7: Enrichment of HP1α and H3K9me3 at telomeres follows the same dynamic as TERRA through the cell cycle.

Change history

  • 27 December 2012

    In the version of this article initially published, the colors in the key in Figure 7c were incorrectly reversed. Red should have represented telomeres and gray α-satellite regions. The error has been corrected in the HTML and PDF versions of the article.

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Acknowledgements

We are grateful to J. Lingner and G. Cristofari (École polytechnique fédérale de Lausanne, Lausanne, Switzerland), T. de Lange (The Rockefeller University, New York, New York, USA), F. Fuks (Université Libre de Bruxelles, Brussels, Belgium), H. Antoine-Poirel (Université catholique de Louvain, Brussels, Belgium) and C. Heirman (Vrije Universiteit Brussel, Brussels, Belgium) for the generous gift of cell lines and plasmids. We thank G. Tilman, A. Loriot and C. De Smet for useful comments on the manuscript and N. Dauguet for technical assistance with flow cytometry. We warmly thank the de Duve Institute for constant support. This work was supported by the Belgian Fonds National de la Recherche Scientifique: Mandat d'Impulsion Scientifique MIS F.4511.09 (to N.A. and A.D.) and by the Fonds pour la formation à la Recherche dans l'Industrie et dans l'Agriculture (FRIA) fellowship FNRS 1.E127.10 (to A.V.B.).

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A.D. and N.A. conceived and planned the project, and wrote the manuscript. N.A. and A.V.B. performed the experiments. N.A., A.V.B. and A.D. analyzed the results.

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Correspondence to Anabelle Decottignies.

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Arnoult, N., Van Beneden, A. & Decottignies, A. Telomere length regulates TERRA levels through increased trimethylation of telomeric H3K9 and HP1α. Nat Struct Mol Biol 19, 948–956 (2012). https://doi.org/10.1038/nsmb.2364

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