Chromatin as a biomolecular condensate

Cells package their genomic DNA into a complex with proteins called chromatin. Chromatin is partitioned into subcompartments that differ from each other with respect to their compaction, molecular composition and biological function. One example are the micron-sized spherical heterochromatin foci that are present in several differentiated cell types and that are readily visible under the microscope. It is a key question how such compartments can form even though diffusion constantly mixes the nuclear interior. One biophysical mechanism that can explain this phenomenon is liquid-liquid phase separation, which drives the formation of liquid droplets around nucleation sites on chromatin. Another one is bridging-induced polymer-polymer phase separation, which condenses chromosomal segments into compact globules. I will briefly discuss these mechanisms and will present recent microscopy-based experiments and computational analyses that assess the properties of condensates in the test tube and of heterochromatin foci in living cells. I will compare these experiments to the different models and touch upon the implications for the dynamic regulation of chromatin subcompartments.

At Amphi Curie and on TEAMS