CpG islands and GC content dictate nucleosome depletion in a transcription-independent manner at mammalian promoters

  1. Jean-Christophe Andrau1,2,3,8
  1. 1Centre d'Immunologie de Marseille-Luminy (CIML), Aix-Marseille University, UM2, Marseille, France;
  2. 2Institut National de la Santé et de la Recherche Médicale (INSERM), U1104, Marseille, France;
  3. 3Centre National de la Recherche Scientifique (CNRS), UMR7280, Marseille, France;
  4. 4TAGC, Case 928, 13288 Marseille cedex 09, France;
  5. 5Centre Nacional D'Anàlisi Genòmica, Parc Científic de Barcelona, Baldiri i Reixac, 08028 Barcelona, Spain
    1. 6 These authors contributed equally to this work.

    • 7 Present address: Department of Developmental Genetics, Max-Planck-Institute for Molecular Genetics, Ihnestraße 63-73, 14195 Berlin, Germany.

    Abstract

    One clear hallmark of mammalian promoters is the presence of CpG islands (CGIs) at more than two-thirds of genes, whereas TATA boxes are only present at a minority of promoters. Using genome-wide approaches, we show that GC content and CGIs are major promoter elements in mammalian cells, able to govern open chromatin conformation and support paused transcription. First, we define three classes of promoters with distinct transcriptional directionality and pausing properties that correlate with their GC content. We further analyze the direct influence of GC content on nucleosome positioning and depletion and show that CpG content and CGI width correlate with nucleosome depletion both in vivo and in vitro. We also show that transcription is not essential for nucleosome exclusion but influences both a weak +1 and a well-positioned nucleosome at CGI borders. Altogether our data support the idea that CGIs have become an essential feature of promoter structure defining novel regulatory properties in mammals.

    Footnotes

    • Received February 8, 2012.
    • Accepted July 24, 2012.

    This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported License), as described at http://creativecommons.org/licenses/by-nc/3.0/.

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