Hyperdynamic plasticity of chromatin proteins in pluripotent embryonic stem cells

Dev Cell. 2006 Jan;10(1):105-16. doi: 10.1016/j.devcel.2005.10.017.

Abstract

Differentiation of embryonic stem (ES) cells from a pluripotent to a committed state involves global changes in genome expression patterns. Gene activity is critically determined by chromatin structure and interactions of chromatin binding proteins. Here, we show that major architectural chromatin proteins are hyperdynamic and bind loosely to chromatin in ES cells. Upon differentiation, the hyperdynamic proteins become immobilized on chromatin. Hyperdynamic binding is a property of pluripotent cells, but not of undifferentiated cells that are already lineage committed. ES cells lacking the nucleosome assembly factor HirA exhibit elevated levels of unbound histones, and formation of embryoid bodies is accelerated. In contrast, ES cells, in which the dynamic exchange of H1 is restricted, display differentiation arrest. We suggest that hyperdynamic binding of structural chromatin proteins is a functionally important hallmark of pluripotent ES cells that contributes to the maintenance of plasticity in undifferentiated ES cells and to establishing higher-order chromatin structure.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Blotting, Western / methods
  • Cell Count / methods
  • Cell Cycle / physiology
  • Cell Cycle Proteins
  • Cell Differentiation / physiology*
  • Cells, Cultured
  • Chromatin / metabolism*
  • Chromatin Assembly and Disassembly / physiology*
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Electrophoresis, Polyacrylamide Gel / methods
  • Embryo, Mammalian
  • Embryonic Development / physiology
  • Gene Expression Regulation, Developmental / physiology
  • Green Fluorescent Proteins / metabolism
  • Histone Chaperones
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase / metabolism
  • Histones / metabolism
  • Immunohistochemistry / methods
  • In Situ Hybridization / methods
  • Indoles
  • Interleukin-6 / deficiency
  • Intermediate Filament Proteins / metabolism
  • Kinetics
  • Leukemia Inhibitory Factor
  • Mice
  • Mice, Knockout
  • Molecular Biology / methods
  • Nerve Tissue Proteins / metabolism
  • Nestin
  • Nonlinear Dynamics
  • Octamer Transcription Factor-3 / metabolism
  • Pluripotent Stem Cells / metabolism*
  • Protein Array Analysis / methods
  • Protein Methyltransferases
  • Time Factors
  • Transcription Factors / deficiency

Substances

  • Cell Cycle Proteins
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • Hira protein, mouse
  • Histone Chaperones
  • Histones
  • Indoles
  • Interleukin-6
  • Intermediate Filament Proteins
  • Leukemia Inhibitory Factor
  • Lif protein, mouse
  • Nerve Tissue Proteins
  • Nes protein, mouse
  • Nestin
  • Octamer Transcription Factor-3
  • Pou5f1 protein, mouse
  • Transcription Factors
  • heterochromatin-specific nonhistone chromosomal protein HP-1
  • Green Fluorescent Proteins
  • DAPI
  • Histone Methyltransferases
  • Protein Methyltransferases
  • Histone-Lysine N-Methyltransferase