Characteristic H3 N-tail dynamics in the nucleosome core particle, nucleosome, and chromatosome

Furukawa, Ayako; Wakamori, Masatoshi; Arimura, Yasuhiro; Ohtomo, Hideaki; Tsunaka, Yasuo; Kurumizaka, Hitoshi; Umehara, Takashi; Nishimura, Yoshifumi

doi:10.1016/j.isci.2022.103937

Cited by 7 publications

(7 citation statements)

References 37 publications

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“…As a result, histone PTMs may play multiple roles; weakening the DNA association to increase access for reader domains, providing a platform for reader domain binding, or both. We note this interaction model is largely based on in vitro studies with single nucleosomes ( Stützer et al, 2016 ; Morrison et al, 2018 ; Rabdano et al, 2021 ; Zhou et al, 2012 ; Musselman and Kutateladze, 2022 ; Ohtomo et al, 2021 ; Ohtomo et al, 2023 ; Zandian et al, 2021 ; Furukawa et al, 2022 ; Jennings et al, 2023 ; Furukawa et al, 2020 ; Morrison et al, 2021 ), and thus does not fully capture the chromatin environment. However, via solid-state NMR spectroscopy, a nearly identical conformation of histone tails has also been observed in chromatin arrays ( Musselman and Kutateladze, 2022 ; Shi et al, 2018 ; Shi et al, 2020 ; Gao et al, 2013 ; Xiang et al, 2018 ), and the H3 tail: DNA interaction has been observed in vivo by ChIP-exo ( Rhee et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Nucleosome conformation dictates the histone code

Marunde,

Fuchs,

Burg

et al. 2024

eLife

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Histone post-translational modifications (PTMs) play a critical role in chromatin regulation. It has been proposed that these PTMs form localized 'codes' that are read by specialized regions (reader domains) in chromatin associated proteins (CAPs) to regulate downstream function. Substantial effort has been made to define [CAP : histone PTM] specificities, and thus decipher the histone code and guide epigenetic therapies. However, this has largely been done using the reductive approach of isolated reader domains and histone peptides, which cannot account for any higher order factors. Here we show that the [BPTF PHD finger and bromodomain : histone PTM] interaction is dependent on nucleosome context. The tandem reader selectively associates with nucleosomal H3K4me3 and H3K14ac or H3K18ac, a combinatorial engagement that despite being in cis is not predicted by peptides. This in vitro specificity of the BPTF tandem reader for PTM-defined nucleosomes is recapitulated in a cellular context. We propose that regulatable histone tail accessibility and its impact on the binding potential of reader domains necessitates we refine the 'histone code' concept and interrogate it at the nucleosome level.

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Section: Discussionmentioning

confidence: 99%

Nucleosome conformation dictates the histone code

Marunde,

Fuchs,

Burg

et al. 2024

eLife

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“…This hypothesis is supported by the fact that the histone tail structures have not been resolved in the three-dimensional structures of nucleosomes determined by X-ray crystallography or cryo-EM analysis. Several studies using NMR have shown multiple types of tail dynamics, , and MD simulations showing intermittent binding of histone tails to nucleosomal DNA , also support this hypothesis. We found that nucleosome dynamics were strongly enhanced in H2B and H3 tail-less nucleosomes because both tails are located at the DNA entry–exit sites of nucleosomes, and their binding/unbinding equilibrium is thought to contribute to the stabilization of nucleosomal DNA around the histone octamer (Figure ).…”

mentioning

confidence: 83%

“…X-ray crystallography and cryo-electron microscopy (cryo-EM) analyses of tail-less nucleosomes revealed a structural deviation of <2 Å in the histone octamer region compared to that of wild-type (WT) nucleosomes. , In addition, nuclear magnetic resonance (NMR) studies , and molecular dynamics (MD) simulations , have shown that histone tails can interact with nucleosomal DNA, linker DNAs, and neighboring nucleosomes. These findings have advanced our understanding of the roles of histone tails in regulating nucleosome dynamics, particularly their interactions with DNA within nucleosomes.…”

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confidence: 99%

High-Speed Atomic Force Microscopy Reveals the Nucleosome Sliding and DNA Unwrapping/Wrapping Dynamics of Tail-less Nucleosomes

Morioka,

Oishi,

Hatazawa

et al. 2024

Nano Lett.

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Each nucleosome contains four types of histone proteins, each with a histone tail. These tails are essential for the epigenetic regulation of gene expression through post-translational modifications (PTMs). However, their influence on nucleosome dynamics at the singlemolecule level remains undetermined. Here, we employed high-speed atomic force microscopy to visualize nucleosome dynamics in the absence of the N-terminal tail of each histone or all of the N-terminal tails. Loss of all tails stripped 6.7 base pairs of the nucleosome from the histone core, and the DNA entry−exit angle expanded by 18°from that of wild-type nucleosomes. Tail-less nucleosomes, particularly those without H2B and H3 tails, showed a 10-fold increase in dynamics, such as nucleosome sliding and DNA unwrapping/wrapping, within 0.3 s, emphasizing their role in histone−DNA interactions. Our findings illustrate that N-terminal histone tails stabilize the nucleosome structure, suggesting that histone tail PTMs modulate nucleosome dynamics.

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“…The histone tails dynamically interact with DNA in a broad ensemble of states. Experimental characterization of nucleosomal H3 tail dynamics began with seminal work by Stützer et al (2016) and studies to date have shown that interactions between the H3 tails and DNA are dynamic on the ps-ns and µs-ms timescales (Stützer et al, 2016;Morrison et al, 2018;Furukawa et al, 2020;Lehmann et al, 2020;Morrison et al, 2021;Zandian et al, 2021;Furukawa et al, 2022). All-atom molecular dynamics simulations have additionally shown dynamic interactions on the ns timescale (Roccatano et al, 2007;Shaytan et al, 2016;Armeev et al, 2021;Peng et al, 2021;Rabdano et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Arginine anchor points govern H3 tail dynamics

Jennings

Zoss

Morrison

2023

Front. Mol. Biosci.

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Chromatin is dynamically reorganized spatially and temporally, and the post-translational modification of histones is a key component of this regulation. The basic subunit of chromatin is the nucleosome core particle, consisting of two copies each of the histones H2A, H2B, H3, and H4 around which ∼147 base pairs of DNA wrap. The intrinsically disordered histone termini, or tails, protrude from the core and are heavily post-translationally modified. Previous studies have shown that the histone tails exist in dynamic ensembles of DNA-bound states within the nucleosome. Histone tail interactions with DNA are involved in nucleosome conformation and chromatin organization. Charge-modulating histone post-translational modifications (PTMs) are poised to perturb the dynamic interactions between histone tails and DNA. Arginine side chains form favorable interactions with DNA and are sites of charge-modulating PTMs such as citrullination. Our current focus is on the H3 tail, the longest histone tail. Four arginine residues are relatively evenly spaced along the H3 tail sequence, suggesting multivalent interactions with DNA poised for regulation by PTMs. In this study, we use NMR nuclear spin relaxation experiments to investigate the contribution of arginine residues to H3 tail dynamics within the nucleosome core particle. By neutralizing arginine via mutation to glutamine, we begin to work towards a comprehensive understanding of the contribution of individual residues to H3 tail dynamics. We find that neutralization of arginine residues results in increased regional mobility of the H3 tails, with implications for understanding the direct effects of arginine citrullination. Altogether, these studies support a role for dynamics within the histone language and emphasize the importance of charge-modulating histone PTMs in regulating chromatin dynamics, starting at the level of the basic subunit of chromatin.

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Characteristic H3 N-tail dynamics in the nucleosome core particle, nucleosome, and chromatosome

Cited by 7 publications

References 37 publications

Nucleosome conformation dictates the histone code

Nucleosome conformation dictates the histone code

High-Speed Atomic Force Microscopy Reveals the Nucleosome Sliding and DNA Unwrapping/Wrapping Dynamics of Tail-less Nucleosomes

Arginine anchor points govern H3 tail dynamics

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