Synthetic CpG islands reveal DNA sequence determinants of chromatin structure

Elisabeth Wachter, Timo Quante, Cara Merusi, Aleksandra Arczewska, Francis Stewart, Shaun Webb, Adrian Bird

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article numbere03397
Number of pages16
Publication statusPublished - 26 Sep 2014


  • bivalent chromatin
  • chromosomes
  • CpG islands
  • DNA methylation
  • genes
  • histone modifications
  • mouse


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