
组蛋白电离性残基的质子化状态变化可以显著影响核小体表面的静电势,从而调节核小体与染色质结合因子的相互作用以及核小体之间的自组装。


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The nucleosome serves as the fundamental unit of chromatin organization, with electrostatic interactions acting as the driving forces in the folding of nucleosomes into chromatin. Perturbations in cellular pH conditions can lead to changes in the protonation states of titratable histone residues, impacting nucleosome surface electrostatic potentials and interactions. However, the effects of proton uptake or release of histone ionizable groups on nucleosome-partner protein interactions and higher-order chromatin structures remain largely unexplored. Here, we conducted comprehensive analyses of histone titratable residue pKa values in various nucleosome contexts, utilizing 96 experimentally determined structures. We revealed that pH-induced changes in histone residue protonation states modulated nucleosome surface electrostatic potentials and significantly influenced nucleosome-partner protein interactions. Furthermore, we observed that proton uptake or release often accompanied nucleosome-partner protein interactions, facilitating their binding processes. Additionally, using a dataset of 1266 recurrent histone cancer mutations, we systematically characterized their impact on nucleosome surface electrostatics, demonstrating their profound effects on electrostatic interactions between nucleosomes and partner proteins. Finally, our findings suggest that alterations in histone protonation or cancer mutations can also regulate nucleosome self-association, thereby modulating the organization and dynamics of higher-order chromatin structure.

### Competing Interest Statement

The authors have declared no competing interest.

Electrostatic interactions in nucleosome and higher-order structures are regulated by protonation state of histone ionizable residue

核小体和高级结构中的静电相互作用受到组蛋白电离性残基质子化状态的调节