Polymer-assisted condensation as key to chromatin localization

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Abstract

We put forward a novel mechanism to account for the experimentally observed positional shifts of chromosomes within the cell nucleus, which appear to be driven by compositional alterations in the nuclear lamina [Science 7 , eabf6251 (2021)]. By considering chromatin as a biomolecular condensate we demonstrate that the adsorption of the chromatin-binding proteins at the lamina leads to a wetting of the condensate while spreading of the chromatin on the lamina is avoided. This leads to the non-monotonous density profile of the polymer with respect to the surface which can be explained by the competition between the tendency of the protein component to wet the surface and the conformational restrictions of the polymer near the impenetrable surface. A change in the composition of the lamina can lead to repositioning of chromatin towards the center of the nucleus. We explore various mechanisms by which lamina compositional shifts could lead to the dewetting of the condensate. Our theory not only offers an explanation for specific chromatin conformation experiments, but also contributes to the broader understanding of wetting onto responsive surfaces in multi-component systems.
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Abstract We put forward a novel mechanism to account for the experimentally observed positional shifts of chromosomes within the cell nucleus, which appear to be driven by compositional alterations in the nuclear lamina [Science 7, eabf6251 (2021)]. By considering chromatin as a biomolecular condensate we demonstrate that the adsorption of the chromatin-binding proteins at the lamina leads to a wetting of the condensate while spreading of the chromatin on the lamina is avoided. This leads to the non-monotonous density profile of the polymer with respect to the surface which can be explained by the competition between the tendency of the protein component to wet the surface and the conformational restrictions of the polymer near the impenetrable surface. A change in the composition of the lamina can lead to repositioning of chromatin towards the center of the nucleus. We explore various mechanisms by which lamina compositional shifts could lead to the dewetting of the condensate. Our theory not only offers an explanation for specific chromatin conformation experiments, but also contributes to the broader understanding of wetting onto responsive surfaces in multi-component systems. Competing Interest Statement The authors have declared no competing interest.

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License: CC-BY-NC-ND-4.0