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

Abstract

We review the mechanism and consequences of the 'bridging-induced attraction', a generic biophysical principle that underpins some existing models for chromosome organization in 3D. 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 that conform well with the observation of A/B compartments in HiC experiments.

Keywords: bridging-induced attraction; microphase separation; nonequilibrium proteins; photobleaching; post-translational modifications; topologically associating domains.