Histone H4 Tails in Nucleosomes: a Fuzzy Interaction with DNA

Overview

Journal Angew Chem Int Ed Engl

Specialty Chemistry

Date 2021 Feb 1

PMID 33522067

Citations 20

Authors

Sevastyan O Rabdano

Matthew D Shannon

Sergei A Izmailov

Nicole Gonzalez Salguero

Mohamad Zandian

Rudra N Purusottam

Michael G Poirier

Nikolai R Skrynnikov

Christopher P Jaroniec

Affiliations

Soon will be listed here.

Abstract

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 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 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).

Citing Articles

Histone N-tails modulate sequence-specific positioning of nucleosomes.

Nikitina T, Guiblet W, Cui F, Zhurkin V J Biol Chem. 2024; 301(2):108138.

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Redox signaling and skeletal muscle adaptation during aerobic exercise.

Zhou Y, Zhang X, Baker J, Davison G, Yan X iScience. 2024; 27(5):109643.

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Nucleosome conformation dictates the histone code.

Marunde M, Fuchs H, Burg J, Popova I, Vaidya A, Hall N Elife. 2024; 13.

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Using NMR diffusion data to validate MD models of disordered proteins: Test case of N-terminal tail of histone H4.

Lebedenko O, Salikov V, Izmailov S, Podkorytov I, Skrynnikov N Biophys J. 2023; 123(1):80-100.

PMID: 37990496 PMC: 10808029. DOI: 10.1016/j.bpj.2023.11.020.

Conformational and Interaction Landscape of Histone H4 Tails in Nucleosomes Probed by Paramagnetic NMR Spectroscopy.

Sun W, Lebedenko O, Salguero N, Shannon M, Zandian M, Poirier M J Am Chem Soc. 2023; 145(46):25478-25485.

PMID: 37943892 PMC: 10719895. DOI: 10.1021/jacs.3c10340.

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