Polymer Biophysics in Chromosome Phase Separation

Intracellular phase separation has recently emerged as a new paradigm in biophysics. Notably, phase separation within chromosomes plays a crucial role in various biological functions, including chromosome organization and the regulation of gene transcription. This process is remarkably complex, involving the condensation of an extraordinarily long DNA molecule‒approximately 2 meters in length within a single cell‒into a micrometer-scale chromosome structure. Despite its significance, the molecular mechanisms underlying phase separation remain poorly understood. Here, we introduce the principles of phase separation and its role in mediating cellular processes. We particularly focus on two molecular models of phase separation: self-association-induced phase separation (SIPS) and bridging-induced phase separation (BIPS). We examine their key properties, compare their mechanisms, and discuss their potential applications in chromosomal biology. Additionally, we delve into the relationship between phase separation and the biological functions of nucleosomes and chromosomes. This special issue provides valuable insights into the polymer physics underlying living systems, offering a foundation for advancing our understanding of intracellular organization and function.