Figure 5.

Liquid–liquid phase separation (LLPS) in chromatin organization. (a–c) Characteristics of droplets formed by LLPS. As shown in panel a, cells contain membrane-less bodies of varying sizes that form through LLPS. These liquid droplets have spherical shapes due to surface tension. As shown in panel b, the size of these liquid droplets scales with the concentration of the component molecules. As shown in panel c, droplets can undergo spontaneous fusion or fission. (d, e) During LLPS, a homogeneous mixture of molecules shown in panel d sorts into two liquid phases, a dense phase with a higher concentration of molecules and a dilute phase surrounding the dense phase shown in panel e. Panel e is an enlargement of the boxed area in panel a. Molecules in liquid phases can rearrange dynamically. (f–i) Chromatin mechanically regulates droplet growth. Droplet growth dynamics can be regulated by the stiffness of surrounding chromatin. Heterochromatin, shown in panel f, is stiffer than euchromatin, shown in panel h, and is less permissive of droplet growth. Growing droplets can, in turn, mechanically deform the surrounding chromatin. Panel g shows an enlargement of the purple boxed area in panel f, while panel i shows an enlargement of the purple boxed area in panel h. (j, k) Super-enhancer (SE) clusters can drive coactivator condensation. As shown in panel j, adjacent enhancers in an SE cluster can nucleate multiple coactivator droplets, where coactivators recruited by transcription factors can phase separate through homotypic polyvalent binding with other coactivators. As shown in panel k, these droplets can coalesce to generate a regulatory hub for transcriptional control of genes without the need for physical juxtaposition of distal enhancers and promoters.