A self-organised liquid reaction container for cellular memory

TL;DR

This paper presents a physical model of a biomolecular condensate acting as a liquid reaction chamber that restores epigenetic marks, stabilizing heterochromatin during cell division through polymer-assisted condensation.

Contribution

It introduces a novel physical model of a biomolecular condensate that promotes epigenetic mark restoration, providing insights into cellular memory mechanisms.

Findings

The condensate stabilizes heterochromatin over multiple cell generations.

Polymer-assisted condensation facilitates droplet formation.

The mechanism is robust and potentially applicable to other epigenetic marks.

Abstract

Epigenetic inheritance during cell division is essential for preserving cell identity by stabilizing the overall chromatin organisation. Heterochromatin,the condensed and transcriptionally silent fraction of chromatin,is marked by specific epigenetic modifications that are diluted during each cell division. Here we build a physical model,based on the formation of a biomolecular condensate,a liquid 'droplet',that promotes the restoration of epigenetic marks. Heterochromatin facilitates the droplet formation via polymer-assisted condensation(PAC). The resulting condensate serves as a reaction chamber to reconstruct the lost epigenetic marks. We incorporate the enzymatic reactions into a particle-based simulation and monitor the progress of the epigenetic markers through an in silico analogue of the cell cycle. We demonstrate that the proposed mechanism is robust and stabilizes the heterochromatin domains over many cell generations. This mechanism and variations thereof might be at work for other epigenetic marks as well.