Electrostatic mechanism of chromatin folding

J Mol Biol. 1990 Feb 20;211(4):883-96. doi: 10.1016/0022-2836(90)90081-V.

Abstract

We describe a theoretical analysis of cation binding in the nucleosome, and in chromatin as it folds, using Manning's polyelectrolyte theory. The theory accounts remarkably well, even quantitatively, both for the interaction of histone charges with DNA in chromatin, and for the essential features of the folding process. The degree of chromatin folding under different ion conditions is reliably predicted by the electrostatic free energy of DNA in the H1 binding site, which determines repulsions between linker DNA segments thus limiting how closely they may approach. The electrostatic free energy is a function of the ionic strength and the residual (unneutralized) DNA charge. Monovalent cations effect chromatin folding primarily by screening the residual charge whilst divalent or trivalent cations bind to DNA reducing its residual charge. The binding of H1 to the linker DNA considerably reduces its electrostatic free energy by displacing bound cations and reducing the residual charge. Thus, native chromatin folds at lower salt concentrations than does H1-depleted chromatin. We conclude that the mechanism of chromatin folding is primarily electrostatic in nature. In vivo ion conditions are such that chromatin is compact but H1 molecules are able to exchange freely, probably due to a low degree of salt-induced dissociation. When H1 molecules exchange, transient local disruptions may occur in the chromatin filament due to repulsion of temporarily H1-free linker DNA from within the filament, such that chromatin "breathes". Thus, the cell can maintain its chromatin in a compact form and access to DNA for sequence-specific DNA-binding proteins and the transcription machinery is still possible.

MeSH terms

  • Animals
  • Cattle
  • Chickens
  • Chromatin / metabolism*
  • Chromatin / ultrastructure
  • DNA / metabolism*
  • Erythrocytes / metabolism
  • Histones / metabolism*
  • Kinetics
  • Magnesium / metabolism
  • Mathematics
  • Models, Theoretical
  • Osmolar Concentration
  • Sodium Chloride / pharmacology
  • Thermodynamics
  • Thymus Gland / metabolism

Substances

  • Chromatin
  • Histones
  • Sodium Chloride
  • DNA
  • Magnesium