Crucial role of dynamic linker histone binding and divalent ions for DNA accessibility and gene regulation revealed by mesoscale modeling of oligonucleosomes

Rosana Collepardo-Guevara, Tamar Schlick

Research output: Contribution to journalArticlepeer-review

Abstract

Monte Carlo simulations of a mesoscale model of oligonucleosomes are analyzed to examine the role of dynamic-linker histone (LH) bindingunbinding in high monovalent salt with divalent ions, and to further interpret noted chromatin fiber softening by dynamic LH in monovalent salt conditions. We find that divalent ions produce a fiber stiffening effect that competes with, but does not overshadow, the dramatic softening triggered by dynamic-LH behavior. Indeed, we find that in typical in vivo conditions, dynamic-LH bindingunbinding reduces fiber stiffening dramatically (by a factor of almost 5, as measured by the elasticity modulus) compared with rigidly fixed LH, and also the force needed to initiate chromatin unfolding, making it consistent with those of molecular motors. Our data also show that, during unfolding, divalent ions together with LHs induce linker-DNA bending and DNA-DNA repulsion screening, which guarantee formation of heteromorphic superbeads-on-a-string structures that combine regions of loose and compact fiber independently of the characteristics of the LH-core bond. These structures might be important for gene regulation as they expose regions of the DNA selectively. Dynamic control of LH bindingunbinding, either globally or locally, in the presence of divalent ions, might constitute a mechanism for regulation of gene expression.

Original languageEnglish (US)
Pages (from-to)8803-8817
Number of pages15
JournalNucleic acids research
Volume40
Issue number18
DOIs
StatePublished - Oct 2012

ASJC Scopus subject areas

  • Genetics

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