Abstract
In the eukaryotic cell nucleus, DNA exists as chromatin, a compact but dynamic complex with histone proteins. The first level of DNA organization is the linear array of nucleosome core particles (NCPs). The NCP is a well-defined complex of 147 bp DNA with an octamer of histones. Interactions between NCPs are of paramount importance for higher levels of chromatin compaction. The polyelectrolyte nature of the NCP implies that nucleosome-nucleosome interactions must exhibit a great influence from both the ionic environment as well as the positively charged and highly flexible N-terminal histone tails, protruding out from the NCP. The large size of the system precludes a modelling analysis of chromatin at an all-atom level and calls for coarse-grained approximations. Here, a model of the NCP that include the globular histone core and the flexible histone tails described by one particle per each amino acid and taking into account their net charge is proposed. DNA wrapped around the histone core was approximated at the level of two base pairs represented by one bead (bases and sugar) plus four beads of charged phosphate groups. Computer simulations, using a Langevin thermostat, in a dielectric continuum with explicit monovalent (K+), divalent (Mg2+) or trivalent (Co(NH3)6 3+) cations were performed for systems with one or ten NCPs. Increase of the counterion charge results in a switch from repulsive NCP-NCP interaction in the presence of K+, to partial aggregation with Mg2+ and to strong mutual attraction of all 10 NCPs in the presence of CoHex3+. The new model reproduced experimental results and the structure of the NCP-NCP contacts is in agreement with available data. Cation screening, ion-ion correlations and tail bridging contribute to the NCP-NCP attraction and the new NCP model accounts for these interactions.
Highlights
In the nucleus of all eukaryotic cells, the carrier of the genetic information, DNA is highly compacted by nuclear proteins into chromatin
It is clear that the polyelectrolyte nature of DNA and the large positive charge of the histones, which neutralize about half of the DNA charge in the nucleosome core particles (NCPs) (Fig. 1) means that the structural and dynamic properties of chromatin are governed by long-range electrostatic interactions with the mobile ions present in the system [15]
Does NCP-NCP attraction appear after substitution of K+ by Mg2+, and full condensation of the NCPs is observed in the presence of CoHex3+, but the geometry of the structure of the NCP-NCP stacking contacts closely matches the X-ray diffraction and electron microscopy observations [23,24]
Summary
In the nucleus of all eukaryotic cells, the carrier of the genetic information, DNA is highly compacted by nuclear proteins into chromatin. The first level of DNA compaction comprises linear domains of DNA-histone complexes, the nucleosomes, which are highly uniform and conserved. Double-stranded linker DNA of variable length connects the NCPs with each other to form a nucleosome array, which is complemented by linker histones and in vitro condenses fibre in a salt-, linker histone-, histone tail-dependent manner [5]. It is clear that the polyelectrolyte nature of DNA and the large positive charge of the histones, which neutralize about half of the DNA charge in the NCP (Fig. 1) means that the structural and dynamic properties of chromatin are governed by long-range electrostatic interactions with the mobile ions present in the system [15]. Rigorous theoretical approaches addressing these electrostatic effects are still lacking, though [15,16]
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