Abstract
Divalent cations such as Mg2+ and Ca2+ are key modulators of chromatin architecture, yet their atomistic influence on nucleosome structure and histone tail dynamics remains elusive. Here, we present 81 microseconds of all-atom molecular dynamics (MD) simulations to dissect how these ions shape nucleosome dynamics and plasticity. We quantitively mapped the selective binding patterns of Mg2+ and Ca2+ in nucleosomes with and without histone tails, revealing distinct ion–nucleosome interactions. Notably, divalent ion binding reduces inter-gyre electrostatic repulsion, facilitates DNA gyre compaction, and increases nucleosome stiffness, as quantified by estimates of the Young’s modulus and correlated motions within specific DNA regions. Importantly, ion binding weakens histone tail–DNA interactions and enhances tail mobility—particularly that of H3—potentially facilitating access by chromatin regulators and tail-mediated chromatin compaction. These findings reveal a dual role of divalent ions in modulating nucleosome plasticity while reinforcing histone tail dynamics, providing a mechanistic framework for understanding how ionic fluctuations influence gene accessibility and chromatin state.
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Data availability
All simulation parameter files, MD trajectories underlying the figures, are available from the Zenodo repository at (https://doi.org/10.5281/zenodo.18232757)89. Processed data used to generate the figures and statistical analyses are included in the same repository. All other data supporting the findings of this study are available from the corresponding author upon reasonable request.
Code availability
All custom analysis scripts used in this study are available from the Zenodo repository at (https://doi.org/10.5281/zenodo.18232757)89. DNA geometry and dynamics were analyzed using AMBER Tools 22 and Bio3D (v2.4.5). Electrostatic analyses were performed using DelPhiForce. Molecular visualization and trajectory inspection were performed using VMD (v1.9.4a) and UCSF Chimera (v1.17.3).
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Acknowledgements
This work was supported by the National Natural Science Foundation of China (No. 12205112), the Natural Science Foundation of Wuhan (No. 2024040801020302) and the self-determined research funds of CCNU from the colleges’ basic research and operation of MOE (CCNU25JC005).
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Y.H.P. conceived and designed the research, performed simulations, analyzed the data, wrote the paper, and acquired funding. G.H.H. performed simulations, analyzed the data, and wrote the paper. W.X., G.G.L., and H.F.Z. contributed to data analysis and interpretation.
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Hu, G., Zhang, H., Xu, W. et al. Selective binding of divalent cations reshapes nucleosome mechanics and unlocks histone tail dynamics. Commun Biol (2026). https://doi.org/10.1038/s42003-026-09648-1
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DOI: https://doi.org/10.1038/s42003-026-09648-1
