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Review
. 2022 Jan 13:8:781981.
doi: 10.3389/fmolb.2021.781981. eCollection 2021.

A Liquid State Perspective on Dynamics of Chromatin Compartments

Rabia Laghmach  1 , Michele Di Pierro  2 , Davit Potoyan  1
Affiliations
Review

A Liquid State Perspective on Dynamics of Chromatin Compartments

Rabia Laghmach et al. Front Mol Biosci. .

Abstract

The interior of the eukaryotic cell nucleus has a crowded and heterogeneous environment packed with chromatin polymers, regulatory proteins, and RNA molecules. Chromatin polymer, assisted by epigenetic modifications, protein and RNA binders, forms multi-scale compartments which help regulate genes in response to cellular signals. Furthermore, chromatin compartments are dynamic and tend to evolve in size and composition in ways that are not fully understood. The latest super-resolution imaging experiments have revealed a much more dynamic and stochastic nature of chromatin compartments than was appreciated before. An emerging mechanism explaining chromatin compartmentalization dynamics is the phase separation of protein and nucleic acids into membraneless liquid condensates. Consequently, concepts and ideas from soft matter and polymer systems have been rapidly entering the lexicon of cell biology. In this respect, the role of computational models is crucial for establishing a rigorous and quantitative foundation for the new concepts and disentangling the complex interplay of forces that contribute to the emergent patterns of chromatin dynamics and organization. Several multi-scale models have emerged to address various aspects of chromatin dynamics, ranging from equilibrium polymer simulations, hybrid non-equilibrium simulations coupling protein binding and chromatin folding, and mesoscopic field-theoretic models. Here, we review these emerging theoretical paradigms and computational models with a particular focus on chromatin's phase separation and liquid-like properties as a basis for nuclear organization and dynamics.

Keywords: chromatin; euchromatin; heterochromatin; imaging; lamin; liquid-liquid phase separation; mesoscale; nuclear organization.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Schematic summary of hierarchical 3D folding of chromatin into compartments and domains. Shown are various keywords relevant for describing nuclear chromatin architecture along with length scales relevant for modeling and imaging studies.
FIGURE 2
FIGURE 2
Predictive polymer models of 3D chromatin folding based on protein binding, loop extrusion and phase separation ideas. Images are adopted from original papers with copyright agreement. From left to right; (A) Michrom Di Pierro et al. (2018), (B) Stringers and Binders Barbieri et al. (2012), (C) Hip-Hop Buckle et al. (2018) and (D) Living Chromatin Jost and Vaillant (2018).
FIGURE 3
FIGURE 3
Mesoscale models of eukaryotic nucleus. Images are adopted from original papers with copyright agreement. From left to right; (A) Mesoscale liquid model of nucleus Laghmach et al. (2020), Laghmach et al., 2021, (B) Magnetic model of chromatin phase separation by Michieletto et al (2019), (C) Mechanical model of stem cell nucleus deformation Tripathi and Menon (2019), and (D) Image based finite element model of nucleus Reynolds et al. (2021).
See this image and copyright information in PMC

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