Theoretical analysis of Polycomb-Trithorax systems predicts that poised chromatin is bistable and not bivalent

Nat Commun. 2019 May 13;10(1):2133. doi: 10.1038/s41467-019-10130-2.


Polycomb (PcG) and Trithorax (TrxG) group proteins give stable epigenetic memory of silent and active gene expression states, but also allow poised states in pluripotent cells. Here we systematically address the relationship between poised, active and silent chromatin, by integrating 73 publications on PcG/TrxG biochemistry into a mathematical model comprising 144 nucleosome modification states and 8 enzymatic reactions. Our model predicts that poised chromatin is bistable and not bivalent. Bivalent chromatin, containing opposing active and silent modifications, is present as an unstable background population in all system states, and different subtypes co-occur with active and silent chromatin. In contrast, bistability, in which the system switches frequently between stable active and silent states, occurs under a wide range of conditions at the transition between monostable active and silent system states. By proposing that bistability and not bivalency is associated with poised chromatin, this work has implications for understanding the molecular nature of pluripotency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatin / metabolism*
  • Chromosomal Proteins, Non-Histone / metabolism
  • Drosophila Proteins / metabolism
  • Enzymes / metabolism
  • Epigenesis, Genetic / physiology*
  • Histone Code / physiology
  • Histone-Lysine N-Methyltransferase / metabolism
  • Histones / metabolism
  • Models, Biological*
  • Myeloid-Lymphoid Leukemia Protein / metabolism
  • Nucleosomes / metabolism
  • Polycomb-Group Proteins / metabolism*


  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • Drosophila Proteins
  • Enzymes
  • Histones
  • KMT2A protein, human
  • Nucleosomes
  • Polycomb-Group Proteins
  • trx protein, Drosophila
  • Myeloid-Lymphoid Leukemia Protein
  • Histone-Lysine N-Methyltransferase