CpG-island promoters drive transcription of human telomeres

  1. Solomon G. Nergadze1,3,
  2. Benjamin O. Farnung2,3,
  3. Harry Wischnewski2,
  4. Lela Khoriauli1,
  5. Valerio Vitelli1,
  6. Raghav Chawla2,
  7. Elena Giulotto1 and
  8. Claus M. Azzalin2
  1. 1Dipartimento di Genetica e Microbiologia Adriano Buzzati-Traverso, Università di Pavia, 2700 Pavia, Italy
  2. 2Institute of Biochemistry, Eidgenössische Technische Hochschule Zürich (ETHZ), CH-8093 Zürich, Switzerland

    1. ↵3 These authors contributed equally to this work.

    Abstract

    The longstanding dogma that telomeres, the heterochromatic extremities of linear eukaryotic chromosomes, are transcriptionally silent was overturned by the discovery that DNA-dependent RNA polymerase II (RNAPII) transcribes telomeric DNA into telomeric repeat-containing RNA (TERRA). Here, we show that CpG dinucleotide-rich DNA islands, shared among multiple human chromosome ends, promote transcription of TERRA molecules. TERRA promoters sustain cellular expression of reporter genes, are located immediately upstream of TERRA transcription start sites, and are bound by active RNAPII in vivo. Finally, the identified promoter CpG dinucleotides are methylated in vivo, and cytosine methylation negatively regulates TERRA abundance. The existence of subtelomeric promoters, driving TERRA transcription from independent chromosome ends, supports the idea that TERRA exerts fundamental functions in the context of telomere biology.

    Keywords:

    Keywords

    Footnotes

    • Reprint requests to: Elena Giulotto, Dipartimento di Genetica e Microbiologia Adriano Buzzati-Traverso, Università di Pavia, 2700 Pavia, Italy; e-mail: elena.giulotto{at}unipv.it; fax: +39-0382-528496; or Claus M. Azzalin, Institute of Biochemistry, Eidgenössische Technische Hochschule Zürich (ETHZ), CH-8093 Zürich, Switzerland; e-mail: claus.azzalin{at}bc.biol.ethz.ch; fax: +41-44-6321298.

    • Article published online ahead of print. Article and publication date are at http://www.rnajournal.org/cgi/doi/10.1261/rna.1748309.

      • Received May 22, 2009.
      • Accepted September 3, 2009.
    | Table of Contents

    This Article

    1. Published in Advance October 22, 2009, doi: 10.1261/rna.1748309 RNA 15: 2186-2194 Copyright © 2009 RNA Society

    Article Category

    Share

    Current Issue

    1. May 2024, 30 (5)
    1. Current Issue
    1. Alert me to new issues of RNA