CpG island-mediated global gene regulatory modes in mouse embryonic stem cells

Nat Commun. 2014 Nov 18;5:5490. doi: 10.1038/ncomms6490.


Both transcriptional and epigenetic regulations are fundamental for the control of eukaryotic gene expression. Here we perform a compendium analysis of >200 large sequencing data sets to elucidate the regulatory logic of global gene expression programs in mouse embryonic stem (ES) cells. We define four major classes of DNA-binding proteins (Core, PRC, MYC and CTCF) based on their target co-occupancy, and discover reciprocal regulation between the MYC and PRC classes for the activity of nearly all genes under the control of the CpG island (CGI)-containing promoters. This CGI-dependent regulatory mode explains the functional segregation between CGI-containing and CGI-less genes during early development. By defining active enhancers based on the co-occupancy of the Core class, we further demonstrate their additive roles in CGI-containing gene expression and cell type-specific roles in CGI-less gene expression. Altogether, our analyses provide novel insights into previously unknown CGI-dependent global gene regulatory modes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line
  • CpG Islands / genetics*
  • DNA Methylation / genetics*
  • DNA-Binding Proteins / classification
  • DNA-Binding Proteins / genetics*
  • Embryonic Stem Cells / cytology*
  • Enhancer Elements, Genetic / genetics
  • Gene Expression Regulation / genetics*
  • Genes, Regulator
  • Mice
  • Polycomb-Group Proteins / genetics
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins c-myc / genetics
  • Sequence Analysis, DNA


  • DNA-Binding Proteins
  • Myc protein, mouse
  • Polycomb-Group Proteins
  • Proto-Oncogene Proteins c-myc

Associated data

  • GEO/GSE48666
  • PDB/E2F4
  • PDB/TIP60