Phase transitions in chromatin: mesoscopic and mean-field approaches

TL;DR

This study uses a minimal physical model to explore how liquid-liquid phase separation and coil-globule transitions influence chromatin organization, revealing nonmonotonic effects on chromatin compaction related to condensate material and size.

Contribution

It introduces a mesoscopic model combining phase separation and polymer physics to analyze chromatin behavior, highlighting the role of condensate material and finite-size effects.

Findings

Radius of gyration varies nonmonotonically with condensate volume fraction.

Polymer collapse and expansion depend on condensate concentration, showing co-non-solvency.

Finite-size effects alter the impact of condensates on different chromatin sizes.

Abstract

By means of a minimal physical model, we investigate the interplay of two phase transitions at play in chromatin organization: (1) liquid-liquid phase separation (LLPS) within the fluid solvating chromatin, resulting in the formation of biocondensates, and (2) the coil-globule crossover of the chromatin fiber, which drives the condensation or extension of the chain. In our model, a species representing a domain of chromatin is embedded in a binary fluid. This fluid phase separates to form a droplet rich in a macromolecule (B). Chromatin particles are trapped in a harmonic potential to reproduce the coil and globular phases of an isolated polymer chain. We investigate the role of the droplet material B on the radius of gyration of this polymer and find that this radius varies nonmonotonically with respect to the volume fraction of B. This behavior is reminiscent of a phenomenon known as $\textit{co-non-solvency}$: a polymer chain in good solvent (S) may collapse when a second good solvent (here B) is added in low quantity, and expand at higher B concentration. Additionally, the presence of finite-size effects on the coil-globule transition results in a qualitatively different impact of the droplet material on polymers of various sizes. In the context of genetic regulation, our results suggest that the size of chromatin domains and the quantity of condensate proteins are key parameters to control whether chromatin may respond to an increase of the quantity of chromatin-binding proteins by condensing or expanding.