NMR-Based Measurements of Site-Specific Electrostatic Potentials of Histone Tails in Nucleosome Core Particles

Electrostatics play a dominant role in guiding many biological processes. This is especially the case in the context of chromatin, where charge interactions modulate diverse activities such as DNA repair, transcription, replication, condensation, and phase separation. Using NMR experiments quantifying solvent paramagnetic relaxation enhancements of backbone amide and side chain methyl protons in the presence of paramagnetic cosolutes and focusing on the nucleosome core particle (NCP), we report near surface electrostatic potentials of tail residues of each of the four histone components of the NCP. These are all negative, despite sequences comprising a high density of positively charged amino acids, emphasizing the strong contribution of the negatively charged DNA with which the tails interact. Changes in electrostatic potentials of as much as 60 mV between isolated histone tails and tails in the context of the NCP are calculated. Notably, the tail potentials can vary significantly from each other, with enrichment in glycine residues correlating with less negative values, highlighting differences in the interactions with DNA.