Role of nucleosome positioning in 3D chromatin organization and loop formation

Kharerin, Hungyo; Bhat, Paike Jayadeva; Padinhateeri, Ranjith

doi:10.1007/s12038-019-9976-1

Cited by 8 publications

(10 citation statements)

References 54 publications

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“…Other features, such as electric charge 76 and the enrichment of macromolecules within phase-separated droplets, may also affect the accessibility of chromatin ensembles. In addition, for more sophisticated models of chromatin accessibility, it would be important to achieve more information about the space-time distribution and structure of genomic regions with a depletion or even complete loss of nucleosomes 77, 78 . To which extent, dense convolutes of naked DNA may exist in the ANC has remained elusive.…”

Section: Discussionmentioning

confidence: 99%

True-to-scale DNA-density maps correlate with major accessibility differences between active and inactive chromatin

Gelléri

Chen

Szczurek

et al. 2022

Preprint

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Chromatin compaction differences may have a strong impact on accessibility of individual macromolecules and macromolecular assemblies to their DNA target sites. Estimates based on fluorescence microscopy with conventional resolution, however, suggested only modest compaction differences (~2-10x) between active and inactive nuclear compartments (ANC and INC). Here, we present maps of nuclear landscapes with true-to-scale DNA-densities, ranging from <5 Mbp/μm3 to >300 Mbp/μm3. Maps were generated from individual human and mouse cell nuclei with single-molecule localization microscopy at ~20 nm lateral and ~100 nm axial resolution and supplemented by electron spectroscopic imaging. Live cell microinjection experiments with 20 nm and 40 nm sized fluorescent beads, corresponding to macromolecular assemblies for transcription and replication, indicated movements within the ANC, but exclusion from the INC. In line with previous studies of transcription, pulse-chase labeling experiments of DNA demonstrated replication within the ANC, followed by re-location of replicated, inactive chromatin into the INC.

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Section: Discussionmentioning

confidence: 99%

True-to-scale DNA-density maps correlate with major accessibility differences between active and inactive chromatin

Gelléri

Chen

Szczurek

et al. 2022

Preprint

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“…In “bottom–up causation” lower levels affect higher levels, whereas in “top–down causation” higher levels of organization can have causal effect on lower levels. In vitro and in silico studies have demonstrated bottom–up causation of chromatin organization by showing that changes in linker length between successive nucleosomes can result in change in folding of the chromatin fiber ( 44 , 45 , 46 , 47 , 48 , 49 ). However, in a hierarchical structure, the formation of higher levels of organization can in turn modulate underlying levels of organization, top–down causation, which has not been explored in 3D chromatin organization.…”

Section: Discussionmentioning

confidence: 99%

Disruption of polyhomeotic polymerization decreases nucleosome occupancy and alters genome accessibility

et al. 2023

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Chromatin attains its three-dimensional (3D) conformation by establishing contacts between different noncontiguous regions. Sterile Alpha Motif (SAM)–mediated polymerization of the polyhomeotic (PH) protein regulates subnuclear clustering of Polycomb Repressive Complex 1 (PRC1) and chromatin topology. The mutations that perturb the ability of the PH to polymerize, disrupt long-range chromatin contacts, alter Hox gene expression, and lead to developmental defects. To understand the underlying mechanism, we combined the experiments and theory to investigate the effect of this SAM domain mutation on nucleosome occupancy and accessibility on a genome wide scale. Our data show that disruption of PH polymerization because of SAM domain mutation decreases nucleosome occupancy and alters accessibility. Polymer simulations investigating the interplay between distant chromatin contacts and nucleosome occupancy, both of which are regulated by PH polymerization, suggest that nucleosome density increases when contacts between different regions of chromatin are established. Taken together, it appears that SAM domain–mediated PH polymerization biomechanically regulates the organization of chromatin at multiple scales from nucleosomes to chromosomes and we suggest that higher order organization can have a top–down causation effect on nucleosome occupancy.

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“…Specifically, the density of chromatin and therefore histone occupancy have been found to be specific for hetero- and euchromatin [ 2 ]. In addition, physical 3D contacts between distant chromatin segments were recently found to be relevant for transcriptional regulation in eukaryotes [ 3 ]. The physical bending properties of the chromatin polymer is an important factor that can support or repress the formation of chromatin loops necessary for these contacts, e.g., by shifting the energetic costs to bend the chromatin into a loop configuration.…”

Section: Introductionmentioning

confidence: 99%

“…The physical bending properties of the chromatin polymer is an important factor that can support or repress the formation of chromatin loops necessary for these contacts, e.g., by shifting the energetic costs to bend the chromatin into a loop configuration. Furthermore, the length and exit angle of linker DNA between histones also seems to play a key role in determining this 3D organization of chromatin [ 3 ]. Not bound to histones, the bare linker DNA has a strong negative electric charge.…”

Section: Introductionmentioning

confidence: 99%

“…Not bound to histones, the bare linker DNA has a strong negative electric charge. The resulting repulsive forces between DNA segments in combination with the relatively stiff A+T rich sequences, which linker DNA often consist of, lead to very stiff and often intrinsically bent chromatin segments [ 3 ]. Taken together, the specific physical properties of linker DNA and influences of histone occupancy on physical properties of chromatin are crucial determinants of 3D chromatin organization and thus transcriptional regulation.…”

Section: Introductionmentioning

confidence: 99%

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Moderation of Structural DNA Properties by Coupled Dinucleotide Contents in Eukaryotes

Sievers

Sauer

Bisch

et al. 2023

Genes

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Dinucleotides are known as determinants for various structural and physiochemical properties of DNA and for binding affinities of proteins to DNA. These properties (e.g., stiffness) and bound proteins (e.g., transcription factors) are known to influence important biological functions, such as transcription regulation and 3D chromatin organization. Accordingly, the question arises of how the considerable variations in dinucleotide contents of eukaryotic chromosomes could still provide consistent DNA properties resulting in similar functions and 3D conformations. In this work, we investigate the hypothesis that coupled dinucleotide contents influence DNA properties in opposite directions to moderate each other’s influences. Analyzing all 2478 chromosomes of 155 eukaryotic species, considering bias from coding sequences and enhancers, we found sets of correlated and anti-correlated dinucleotide contents. Using computational models, we estimated changes of DNA properties resulting from this coupling. We found that especially pure A/T dinucleotides (AA, TT, AT, TA), known to influence histone positioning and AC/GT contents, are relevant moderators and that, e.g., the Roll property, which is known to influence histone affinity of DNA, is preferably moderated. We conclude that dinucleotide contents might indirectly influence transcription and chromatin 3D conformation, via regulation of histone occupancy and/or other mechanisms.

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Role of nucleosome positioning in 3D chromatin organization and loop formation

Cited by 8 publications

References 54 publications

True-to-scale DNA-density maps correlate with major accessibility differences between active and inactive chromatin

True-to-scale DNA-density maps correlate with major accessibility differences between active and inactive chromatin

Disruption of polyhomeotic polymerization decreases nucleosome occupancy and alters genome accessibility

Moderation of Structural DNA Properties by Coupled Dinucleotide Contents in Eukaryotes

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