Large histone H3 lysine 9 dimethylated chromatin blocks distinguish differentiated from embryonic stem cells

Nat Genet. 2009 Feb;41(2):246-50. doi: 10.1038/ng.297. Epub 2009 Jan 18.


Higher eukaryotes must adapt a totipotent genome to specialized cell types with stable but limited functions. One potential mechanism for lineage restriction is changes in chromatin, and differentiation-related chromatin changes have been observed for individual genes. We have taken a genome-wide view of histone H3 lysine 9 dimethylation (H3K9Me2) and find that differentiated tissues show surprisingly large K9-modified regions (up to 4.9 Mb). These regions are highly conserved between human and mouse and are differentiation specific, covering only approximately 4% of the genome in undifferentiated mouse embryonic stem (ES) cells, compared to 31% in differentiated ES cells, approximately 46% in liver and approximately 10% in brain. These modifications require histone methyltransferase G9a and are inversely related to expression of genes within the regions. We term these regions large organized chromatin K9 modifications (LOCKs). LOCKs are substantially lost in cancer cell lines, and they may provide a cell type-heritable mechanism for phenotypic plasticity in development and disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Validation Study

MeSH terms

  • Animals
  • Brain / metabolism
  • Cell Differentiation*
  • Cells, Cultured
  • Chromosome Mapping
  • Embryonic Stem Cells / metabolism
  • Embryonic Stem Cells / physiology*
  • Gene Knockdown Techniques
  • HCT116 Cells
  • HeLa Cells
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase
  • Histones / chemistry
  • Histones / metabolism*
  • Humans
  • Liver / metabolism
  • Lysine / metabolism*
  • Mice
  • Models, Biological
  • Organ Specificity
  • Protein Methyltransferases / metabolism*
  • Protein Processing, Post-Translational / physiology


  • Histones
  • Histone Methyltransferases
  • Protein Methyltransferases
  • Histone-Lysine N-Methyltransferase
  • Lysine

Associated data

  • GEO/GSE13445