1. Chromosomes and Gene Expression
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Synthetic CpG islands reveal DNA sequence determinants of chromatin structure

  1. Elisabeth Wachter
  2. Timo Quante
  3. Cara Merusi
  4. Aleksandra Arczewska
  5. Francis Stewart
  6. Shaun Webb
  7. Adrian Bird  Is a corresponding author
  1. University of Edinburgh, United Kingdom
  2. Technische Universitaet Dresden, Germany
Research Article
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Cite this article as: eLife 2014;3:e03397 doi: 10.7554/eLife.03397

Abstract

The mammalian genome is punctuated by CpG islands (CGIs), which differ sharply from the bulk genome by being rich in G+C and the dinucleotide CpG. CGIs often include transcription initiation sites and display 'active' histone marks, notably histone H3 lysine 4 methylation. In embryonic stem cells (ESCs) some CGIs adopt a 'bivalent' chromatin state bearing simultaneous 'active' and 'inactive' chromatin marks. To determine whether CGI chromatin is developmentally programmed at specific genes or is imposed by shared features of CGI DNA, we integrated artificial CGI-like DNA sequences into the ESC genome. We found that bivalency is the default chromatin structure for CpG-rich, G+C-rich DNA. A high CpG density alone is not sufficient for this effect, as A+T-rich sequence settings invariably provoke de novo DNA methylation leading to loss of CGI signature chromatin. We conclude that both CpG-richness and G+C-richness are required for induction of signature chromatin structures at CGIs.

Article and author information

Author details

  1. Elisabeth Wachter

    University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Timo Quante

    University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Cara Merusi

    University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Aleksandra Arczewska

    University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Francis Stewart

    Technische Universitaet Dresden, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Shaun Webb

    University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Adrian Bird

    University of Edinburgh, Edinburgh, United Kingdom
    For correspondence
    A.Bird@ed.ac.uk
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Anne C Ferguson-Smith, University of Cambridge, United Kingdom

Publication history

  1. Received: May 16, 2014
  2. Accepted: September 11, 2014
  3. Accepted Manuscript published: September 26, 2014 (version 1)
  4. Version of Record published: October 21, 2014 (version 2)

Copyright

© 2014, Wachter et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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Further reading

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