CpG Islands Shape the Epigenome Landscape

J Mol Biol. 2021 Mar 19;433(6):166659. doi: 10.1016/j.jmb.2020.09.018. Epub 2020 Oct 1.


Epigenetic modifications and nucleosome positioning play an important role in modulating gene expression. However, how the patterns of epigenetic modifications and nucleosome positioning are established around promoters is not well understood. Here, we have addressed these questions in a series of genome-wide experiments coupled to a novel bioinformatic analysis approach. Our data reveal a clear correlation between CpG density, promoter activity and accumulation of active or repressive histone marks. CGI boundaries define the chromatin promoter regions that will be epigenetically modified. CpG-rich promoters are targeted by histone modifications and histone variants, while CpG-poor promoters are regulated by DNA methylation. CGIs boundaries, but not transcriptional activity, are essential determinants of H2A.Z positioning in vicinity of the promoters, suggesting that the presence of H2A.Z is not related to transcriptional control. Accordingly, H2A.Z depletion has no impact on gene expression of arrested mouse embryonic fibroblasts. Therefore, the underlying DNA sequence, the promoter CpG density and, to a lesser extent, transcriptional activity, are key factors implicated in promoter chromatin architecture.

Keywords: epigenetic modifications; histone variant H2A.Z; nucleosome positioning; promoter chromatin organization; transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromatin / metabolism
  • Chromatin / ultrastructure
  • Chromatin Assembly and Disassembly
  • Computational Biology / methods
  • CpG Islands*
  • DNA Methylation
  • Embryo, Mammalian
  • Epigenesis, Genetic*
  • Epigenome*
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Histones / chemistry
  • Histones / deficiency
  • Histones / genetics*
  • Histones / metabolism
  • Mice
  • Mice, Knockout
  • Primary Cell Culture
  • Promoter Regions, Genetic*
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Processing, Post-Translational*


  • Chromatin
  • H2az1 protein, mouse
  • Histones
  • Protein Isoforms