Electrostatic mechanism of nucleosomal array folding revealed by computer simulation

Jian Sun, Qing Zhang, Tamar Schlick

Research output: Contribution to journalArticle

Abstract

Although numerous experiments indicate that the chromatin fiber displays salt-dependent conformations, the associated molecular mechanism remains unclear. Here, we apply an irregular Discrete Surface Charge Optimization (DiSCO) model of the nucleosome with all histone tails incorporated to describe by Monte Carlo simulations salt-dependent rearrangements of a nucleosomal array with 12 nucleosomes. The ensemble of nucleosomal array conformations display salt-dependent condensation in good agreement with hydrodynamic measurements and suggest that the array adopts highly irregular 3D zig-zag conformations at high (physiological) salt concentrations and transitions into the extended "beads-on-a-string" conformation at low salt. Energy analyses indicate that the repulsion among linker DNA leads to this extended form, whereas internucleosome attraction drives the folding at high salt. The balance between these two contributions determines the salt-dependent condensation. Importantly, the internucleosome and linker DNA-nucleosome attractions require histone tails; we find that the H3 tails, in particular, are crucial for stabilizing the moderately folded fiber at physiological monovalent salt.

Original languageEnglish (US)
Pages (from-to)8180-8185
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number23
DOIs
StatePublished - Jun 7 2005

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Static Electricity
Computer Simulation
Salts
Nucleosomes
Histones
Molecular Conformation
DNA
Hydrodynamics
Chromatin

Keywords

  • Chromatin modeling
  • Discrete Surface Charge Optimization model
  • Irregular 3D zig-zag

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Electrostatic mechanism of nucleosomal array folding revealed by computer simulation. / Sun, Jian; Zhang, Qing; Schlick, Tamar.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 23, 07.06.2005, p. 8180-8185.

Research output: Contribution to journalArticle

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