Bridging-induced microphase separation: photobleaching experiments, chromatin domains, and the need for active reactions

TL;DR

This paper reviews the bridging-induced attraction mechanism in chromatin organization, explaining how multivalent proteins drive nuclear body formation and chromatin domains through microphase separation, supported by simulations and experimental observations.

Contribution

It highlights the role of bridging-induced attraction in chromosome organization and incorporates active reactions to explain dynamic cluster behavior, linking simulations with experimental data.

Findings

Bridging-induced attraction explains nuclear body formation.

Clusters exhibit fast dynamics consistent with photobleaching experiments.

Chromatin domains from simulations match A/B compartments observed in HiC data.

Abstract

We review the mechanism and consequences of the "bridging-induced attraction", a generic biophysical principle which underpins some existing models for chromosome organisation in 3-D. This attraction, which was revealed in polymer physics-inspired computer simulations, is a generic clustering tendency arising in multivalent chromatin-binding proteins, and it provides an explanation for the biogenesis of nuclear bodies and transcription factories via microphase separation. Including post-translational modification reactions involving these multivalent proteins can account for the fast dynamics of the ensuing clusters, as is observed via microscopy and photobleaching experiments. The clusters found in simulations also give rise to chromatin domains which conform well with the observation of A/B compartments in HiC experiments.