Abstract
Chromatin condensation is driven by the energetically favourable interaction between nucleosome core particles (NCPs). The close NCP-NCP contact, stacking, is a primary structural element of all condensed states of chromatin in vitro and in vivo. However, the molecular structure of stacked nucleosomes as well as the nature of the interactions involved in its formation have not yet been systematically studied. Here we undertake an investigation of both the structural and physico-chemical features of NCP structure and the NCP-NCP stacking. We introduce an “NCP-centred” set of parameters (NCP-NCP distance, shift, rise, tilt, and others) that allows numerical characterisation of the mutual positions of the NCPs in the stacking and in any other structures formed by the NCP. NCP stacking in more than 140 published NCP crystal structures were analysed. In addition, coarse grained (CG) MD simulations modelling NCP condensation was carried out. The CG model takes into account details of the nucleosome structure and adequately describes the long range electrostatic forces as well as excluded volume effects acting in chromatin. The CG simulations showed good agreement with experimental data and revealed the importance of the H2A and H4 N-terminal tail bridging and screening as well as tail-tail correlations in the stacked nucleosomes.
Highlights
About 85% of DNA in chromatin exists in the form of regular protein-DNA complexes called nucleosomes[1]
Combining the information extracted from the analysis of nucleosome core particles (NCPs)-NCP contacts in the crystals with results of our GC Langevin molecular dynamics (MD) computer simulations of NCP self-association, we reveal and discuss the electrostatic forces responsible for nucleosome interactions
The progress in cryo-electron microscopy (cryo-electron microscopy (EM)) microscopy has resulted in determination of the atomic or nearly atomic resolution structures of single NCP53–55, NCP with linker histones[38] and nucleosome arrays[39]
Summary
About 85% of DNA in chromatin exists in the form of regular protein-DNA complexes called nucleosomes[1]. Chromatin at the first level of its organization is a linear array of uniform structural units, nucleosomes, formed by 150–210 base pair (bp) of double stranded (ds) DNA and an octamer of highly conserved histone proteins. The positively charged histone tails interact with the negatively charged DNA of its own NCP and with neighbouring nucleosomes, with the linker DNA, and with other non-histone nuclear proteins[6,21,22]. These functions of the histone tails may be modified by covalent post-translational modifications of its amino acids. Single molecule measurements demonstrate that the nucleosome-nucleosome stacking is energetically favourable[29,42,43,44,45]
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