Histone 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 15N NM...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2021-03, Vol.60 (12), p.6480-6487
Main Authors: Rabdano, Sevastyan O., Shannon, Matthew D., Izmailov, Sergei A., Gonzalez Salguero, Nicole, Zandian, Mohamad, Purusottam, Rudra N., Poirier, Michael G., Skrynnikov, Nikolai R., Jaroniec, Christopher P.
Format: Article
Language:English
Subjects:
Bonding strength
Chromatin remodeling
Deoxyribonucleic acid
DNA
DNA - chemistry
fuzzy protein–DNA interactions
Histone H4
histone tails
Histones
Histones - chemistry
Hydrogen bonding
Hydrogen bonds
Ionic strength
molecular dynamics
NMR
NMR spectroscopy
Nuclear magnetic resonance
nucleosome
Nucleosomes
Nucleosomes - chemistry
Protein structure
Sodium chloride
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Summary: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 15N 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 on conformational dynamics of histone tails. Our findings indicate that histone H4 tails engage in a fuzzy interaction with nucleosomal DNA, underpinned by a variable pattern of short‐lived salt bridges and hydrogen bonds, which persists at low ionic strength (0–100 mM NaCl). 15N relaxation data suggest that amino‐terminal histone H4 tails in reconstituted nucleosome are flexible. This result is rationalized by suitably designed MD simulations, showing that H4 tails are involved in a fuzzy interaction with nucleosomal DNA while retaining their disordered character.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.202012046