Polymer physics of chromosome spatial organization.

In the nucleus of cells, chromosomes have been discovered to self-organize into a complex spatial architecture that serves vital functional purposes as, for instance, genes have to establish specific physical contacts with their distal DNA regulators to control transcriptional activities. However, how the system self-assembles to shape the folding of our genome and its functions is only poorly understood. In this talk, I discuss principled models of interacting polymers from statistical mechanics to investigate the mechanisms whereby distal DNA sequences recognize and interact with each other. By combining polymer physics theory and computer simulations, I show that chromosome spatial organization is controlled at the single-molecule level by thermodynamic mechanisms of phase-separation transitions, which spontaneously establish contact or segregation between specific genomic sites, such as genes and their regulators. Those theories are validated against independent experiments, opening to new tools for real-world applications, such as the prediction of the effects of disease-associated mutations, linked to congenital disorders or cancer, on genome 3D structure.