Recent work has raised awareness among cell biologists about how biophysical phenomena such as liquid-liquid phase separation (LLPS can arise from networks of molecular interactions within cells. Phase separation can account for ‘self-assembly’ of functional components that are compartmentalized into bodies without constraining membranes, such as nucleoli, similar to the way mixtures of oil and water ultimately separate into distinct pools. Importantly, these phase systems display ‘emergent properties’ observed in vivo, e.g., liquid droplet behavior, anomalous diffusion and selective permeability, that could play important roles in cellular organization and functions.
We previously demonstrated that formation of one important chromatin domain, called heterochromatin, depends on phase separation in fruit flies and mammals (Strom et al., Nature 2017). I will describe the in vitro and in vivo evidence that supports this conclusion, as well as recent progress on elucidating the critical components and interactions responsible for LLPS of heterochromatin in vivo (Lee et al. PLoS Genetics 2020). I will then focus on how we are addressing a key question; is LLPS, and associated properties such as liquidity, directly required for heterochromatin organization, functions and dynamics? Finally, I will discuss how phase separation and associated emergent properties could more generally dramatically impact our understanding of genome organization, dynamics and functions.