Chromatin domains in the cell: Phase separation and condensation

Negatively charged genomic DNA wraps around positively charged core histone octamers to form nucleosomes, which, along with proteins and RNAs, self-organize into chromatin within the nucleus. In eukaryotic cells, chromatin forms loops that collapse into chromatin domains and serve as functional units of the genome. Chromatin domains vary in physical properties based on gene activity and are assembled into A (euchromatin) and B (heterochromatin) compartments. Since various factors-such as chromatin-binding proteins, histone modifications, transcriptional states, depletion attraction, and cations-can significantly impact chromatin organization, the formation processes of these hierarchical structures remain unclear. No single imaging, genomics, or modeling method can provide a complete picture of the process. Beautiful models can sometimes fool our thinking. In this short review, we critically discuss the formation mechanisms of the chromatin domain in the cell from a physical point of view, including phase separation and condensation.