Emergent domain segregation in self-interacting polymers explains chromosome 3D conformations in single human cells.

Abstract

Polymer physics models have been employed to elucidate the 3D organization of chromosomes in the cell nucleus. However, how well they capture chromatin architectures at the single-molecule level remains poorly understood. Here, we consider a minimal polymer model where folding is driven by sequence-specific self-interactions between cognate monomer types, leading to their separation into spatially segregated globular domains. Focusing on a key genomic region in human IMR90 cells, we demonstrate that the model accurately reproduces the distribution of individual chromatin conformations as validated by single-cell super-resolution microscopy experiments. The structural variability across cells is naturally explained by the predicted thermodynamic ensemble of domain-segregated states, hence providing a robust validation of the model basic ingredients with no additional molecular parameters.