Topological polymorphism of nucleosome fibers and folding of chromatin

Zhurkin, Victor B.; Norouzi, Davood

doi:10.1016/j.bpj.2021.01.008

Cited by 19 publications

(11 citation statements)

References 78 publications

(194 reference statements)

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“…Similar to previous structures of nucleosome arrays 23 , 25 , 26 , the structures presented here use NRLs that correspond to those found in vivo 7 and that differ by integer repeats of the approximate helical repeat of DNA (10n bp linkers with n being a natural number). However, alternative structures of trinucleosomes and tetranucleosomes certainly exist in vivo, and it will be important to study arrays with other linker lengths in the future 43 .…”

Section: Discussionmentioning

confidence: 99%

Histone H1 binding to nucleosome arrays depends on linker DNA length and trajectory

Dombrowski¹,

Engeholm²,

Dienemann³

et al. 2022

Nat Struct Mol Biol

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Throughout the genome, nucleosomes often form regular arrays that differ in nucleosome repeat length (NRL), occupancy of linker histone H1 and transcriptional activity. Here, we report cryo-EM structures of human H1-containing tetranucleosome arrays with four physiologically relevant NRLs. The structures show a zig-zag arrangement of nucleosomes, with nucleosomes 1 and 3 forming a stack. H1 binding to stacked nucleosomes depends on the NRL, whereas H1 always binds to the non-stacked nucleosomes 2 and 4. Short NRLs lead to altered trajectories of linker DNA, and these altered trajectories sterically impair H1 binding to the stacked nucleosomes in our structures. As the NRL increases, linker DNA trajectories relax, enabling H1 contacts and binding. Our results provide an explanation for why arrays with short NRLs are depleted of H1 and suited for transcription, whereas arrays with long NRLs show full H1 occupancy and can form transcriptionally silent heterochromatin regions.

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Section: Discussionmentioning

confidence: 99%

Histone H1 binding to nucleosome arrays depends on linker DNA length and trajectory

Dombrowski¹,

Engeholm²,

Dienemann³

et al. 2022

Nat Struct Mol Biol

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“…In partnership, mechanistic computational models 79 can generate hypotheses and link them to the physicochemical properties of chromatin. A wide range of mechanistic coarse-grained models with nucleosome and subnucleosome resolution have been developed in the past few years 8,9,15,21,29,30,[80][81][82][83][84][85][86][87][88][89][90][91][92][93][94][95][96][97] to bridge molecular and physicochemical information of nucleosomes to the mesoscale properties of chromatin. Future integration of both data-driven polymer models with mechanistic chromatin descriptions holds great potential for providing a complete view of chromatin organization.…”

mentioning

confidence: 99%

Nucleosome plasticity is a critical element of chromatin liquid–liquid phase separation and multivalent nucleosome interactions

et al. 2021

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Liquid–liquid phase separation (LLPS) is an important mechanism that helps explain the membraneless compartmentalization of the nucleus. Because chromatin compaction and LLPS are collective phenomena, linking their modulation to the physicochemical features of nucleosomes is challenging. Here, we develop an advanced multiscale chromatin model—integrating atomistic representations, a chemically-specific coarse-grained model, and a minimal model—to resolve individual nucleosomes within sub-Mb chromatin domains and phase-separated systems. To overcome the difficulty of sampling chromatin at high resolution, we devise a transferable enhanced-sampling Debye-length replica-exchange molecular dynamics approach. We find that nucleosome thermal fluctuations become significant at physiological salt concentrations and destabilize the 30-nm fiber. Our simulations show that nucleosome breathing favors stochastic folding of chromatin and promotes LLPS by simultaneously boosting the transient nature and heterogeneity of nucleosome–nucleosome contacts, and the effective nucleosome valency. Our work puts forward the intrinsic plasticity of nucleosomes as a key element in the liquid-like behavior of nucleosomes within chromatin, and the regulation of chromatin LLPS.

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“…In contrast to the regularly ordered chromatin arrays observed by X-ray crystallography and cryo-electron microscopy in vitro (Schalch et al, 2005;Song et al, 2014;Ekundayo et al, 2017;Garcia-Saez et al, 2018;Adhireksan et al, 2020;Zhou et al, 2021b), chromatin in vivo appears to be very heterogeneous. In vitro experiments and molecular dynamics simulations suggest that nucleosome arrays can adapt a wide variety of conformations Mauney et al, 2021;Ding et al, 2021;Zhurkin and Norouzi, 2021) with some enriched local configurations such as stacked nucleosomes (Mauney et al, 2021;Ding et al, 2021). Indeed, while there is evidence for regularly folded chromatin fibers in terminally differentiated chicken erythrocyte nuclei (Scheffer et al, 2011), most chromatin in or ex vivo seems to have no apparent order (Eltsov et al, 2008;Nishino et al, 2012;Chen et al, 2016;Ou et al, 2017;Cai et al, 2018;Xu et al, 2021;Beel et al, 2021).…”

Section: Nucleosome Organization In Vivomentioning

confidence: 99%

“…with n, x ∈ N and 0 ≤ x ≤ 9. Simulations suggest different topologies for 10n and 10n+5 fibers and conversion between the two topological states likely necessitates topoisomerase activity (Zhurkin and Norouzi, 2021). There are indications that 10n+5 fibers favor less compact chromatin and might thus be more transcriptionally active in yeast (Zhurkin and Norouzi, 2021).…”

Section: Nucleosome Arrays Beyond 10nmentioning

confidence: 99%

“…Simulations suggest different topologies for 10n and 10n+5 fibers and conversion between the two topological states likely necessitates topoisomerase activity (Zhurkin and Norouzi, 2021). There are indications that 10n+5 fibers favor less compact chromatin and might thus be more transcriptionally active in yeast (Zhurkin and Norouzi, 2021). It is tempting to speculate that the effect of increased H1 binding to longer NRL arrays would also be observed there as with increasing linker length, nucleosomes would move further apart and have less of a restrictive effect on the trajectories of neighboring nucleosomes.…”

Section: Nucleosome Arrays Beyond 10nmentioning

confidence: 99%

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Structural studies of short nucleosome arrays containing linker histone H1

Dombrowski¹

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Topological polymorphism of nucleosome fibers and folding of chromatin

Cited by 19 publications

References 78 publications

Histone H1 binding to nucleosome arrays depends on linker DNA length and trajectory

Histone H1 binding to nucleosome arrays depends on linker DNA length and trajectory

Nucleosome plasticity is a critical element of chromatin liquid–liquid phase separation and multivalent nucleosome interactions

Structural studies of short nucleosome arrays containing linker histone H1

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