The Physical Behavior of Interphase Chromosomes: Polymer Theory and Coarse-Grain Computer Simulations.

Abstract

Fluorescence in situ hybridization and chromosome conformation capture methods point to the same conclusion: that chromosomes appear to the external observer as compact structures with a highly nonrandom three-dimensional organization. In this work, we recapitulate the efforts made by us and other groups to rationalize this behavior in terms of the mathematical language and tools of polymer physics. After a brief introduction dedicated to some crucial experiments dissecting the structure of interphase chromosomes, we discuss at a nonspecialistic level some fundamental aspects of theoretical and numerical polymer physics. Then, we inglobe biological and polymer aspects into a polymer model for interphase chromosomes which moves from the observation that mutual topological constraints, such as those typically present between polymer chains in ordinary melts, induce slow chain dynamics and "constraint" chromosomes to resemble double-folded randomly branched polymer conformations. By explicitly turning these ideas into a multi-scale numerical algorithm which is described here in full details, we can design accurate model polymer conformations for interphase chromosomes and offer them for systematic comparison to experiments. The review is concluded by discussing the limitations of our approach and pointing to promising perspectives for future work.