biostudies-literatureRabdano SOSaint Petersburg State UniversityNational Institutes of HealthRussian Science FoundationNIGMS NIH HHSNIH HHSNational Science Foundation6480-6487https://www.ebi.ac.uk/biostudies/studies/S-EPMC7994933biostudies-literatureUnknown60(12)The interaction of positively charged N-terminal histone tails with nucleosomal DNA plays an important role in chromatin assembly and regulation, modulating their susceptibility to post-translational modifications and recognition by chromatin-binding proteins. Here, we report residue-specific ¹⁵ N NMR relaxation rates for histone H4 tails in reconstituted nucleosomes. These data indicate that H4 tails are strongly dynamically disordered, albeit with reduced conformational flexibility compared to a free peptide with the same sequence. Remarkably, the NMR observables were successfully reproduced in a 2-μs MD trajectory of the nucleosome. This is an important step toward resolving an apparent inconsistency where prior simulations were generally at odds with experimental evidence onAngewandte Chemie (International ed. in English)Histone H4 Tails in Nucleosomes: a Fuzzy Interaction with DNA.PMC7994933MCB-1715174S10 OD012303R01GM12374315-14-20038R01GM118664R01 GM123743S10OD01230351142660R01 GM118664Gonzalez Salguero NJaroniec CPPurusottam RNSkrynnikov NRRabdano SOIzmailov SAShannon MDPoirier MGZandian MfalseHistone H4 Tails in Nucleosomes: a Fuzzy Interaction with DNA.The interaction of positively charged N-terminal histone tails with nucleosomal DNA plays an important role in chromatin assembly and regulation, modulating their susceptibility to post-translational modifications and recognition by chromatin-binding proteins. Here, we report residue-specific ¹⁵ N NMR relaxation rates for histone H4 tails in reconstituted nucleosomes. These data indicate that H4 tails are strongly dynamically disordered, albeit with reduced conformational flexibility compared to a free peptide with the same sequence. Remarkably, the NMR observables were successfully reproduced in a 2-μs MD trajectory of the nucleosome. This is an important step toward resolving an apparent inconsistency where prior simulations were generally at odds with experimental evidence on2021-01-01T00:00:00Z2021 Mar2026-05-31T07:06:26.917Z2025-04-05T09:50:13.695ZS-EPMC79949333352206710.1002/anie.202012046