Electrostatic Origin of Salt-Induced Nucleosome Array Compaction

Abstract

The physical mechanism of the folding and unfolding of chromatin is fundamentally related to transcription but is incompletely characterized and not fully understood. We experimentally and theoretically studied chromatin compaction by investigating the salt-mediated folding of an array made of 12 positioning nucleosomes with 177 bp repeat length. Sedimentation velocity measurements were performed to monitor the folding provoked by addition of cations Na(+), K(+), Mg(2+), Ca(2+), spermidine(3+), Co(NH(3))(6)(3+), and spermine(4+). We found typical polyelectrolyte behavior, with the critical concentration of cation needed to bring about maximal folding covering a range of almost five orders of magnitude (from 2 μM for spermine(4+) to 100 mM for Na(+)). A coarse-grained model of the nucleosome array based on a continuum dielectric description and including the explicit presence of mobile ions and charged flexible histone tails was used in computer simulations to investigate the cation-mediated compaction. The results of the simulations with explicit ions are in general agreement with the experimental data, whereas simple Debye-Hückel models are intrinsically incapable of describing chromatin array folding by multivalent cations. We conclude that the theoretical description of the salt-induced chromatin folding must incorporate explicit mobile ions that include ion correlation and ion competition effects.

Electrostatic interactions in biological DNA-related systems

“…With all these complications for analytical modelling in mind, extensive computer simulations of fiber formation performed in recent years, [366][367][368][369][370] provide a comprehensive complementary coverage on several intricate issues. With a growing computer power, nowadays, more fine and important details of NCP structure can be incorporated in largescale fiber simulations, rendering them more instructive and probably superior to analytical, ''model'' calculations with their limited applicability regimes.…”

A Coarse-Grained DNA Model Parameterized from Atomistic Simulations by Inverse Monte Carlo

“…We have previously performed modeling of an NCP solution [38,47] and of a chromatin fiber (a nucleosome array) [53][54][55]. These simplified coarse-grained continuum electrostatic simulation models were successfully applied to qualitatively reproduce histone tail-mediated chromatin folding and nucleosome core particle aggregation [38,47,54] induced by multivalent cations.…”

“…These simplified coarse-grained continuum electrostatic simulation models were successfully applied to qualitatively reproduce histone tail-mediated chromatin folding and nucleosome core particle aggregation [38,47,54] induced by multivalent cations. Long-range electrostatic interactions were included by the presence of explicit mobile ions (representing the salt), but using a simplified structural model of the NCP and of the charge distribution on the array.…”

Structure-driven homology pairing of chromatin fibers: the role of electrostatics and protein-induced bridging

“…A number of experimental [30][31][32][33], theoretical [34][35][36], and computer simulation studies [37][38][39][40][41][42][43][44][45] have emerged on this subject in recent years. Chromatin 30-nm fibers interact electrostatically with each other via "contacting" NCPs positioned on the fiber periphery, both in canonical solenoidal [46,47] and crosslinked [34] fiber models.…”