Shape Transitions and Chiral Symmetry Breaking in the Energy Landscape of the Mitotic Chromosome

TL;DR

This paper develops an unbiased energy landscape model for metaphase chromosomes that reproduces experimental contact probabilities and reveals spontaneous chiral symmetry breaking leading to helical structures, influenced by TAD interactions.

Contribution

It introduces a maximum entropy based energy landscape for chromosomes that captures their structural and chiral properties, integrating TAD interactions for realistic modeling.

Findings

Chromosomes form helical, liquid crystalline structures in simulations.

Chiral symmetry breaking occurs spontaneously, with left or right handed twists.

TAD interactions influence the stability and phase diagram of chromosome structures.

Abstract

We derive an unbiased information theoretic energy landscape for chromosomes at metaphase using a maximum entropy approach that accurately reproduces the details of the experimentally measured pair-wise contact probabilities between genomic loci. Dynamical simulations using this landscape lead to cylindrical, helically twisted structures reflecting liquid crystalline order. These structures are similar to those arising from a generic ideal homogenized chromosome energy landscape. The helical twist can be either right or left handed so chiral symmetry is broken spontaneously. The ideal chromosome landscape when augmented by interactions like those leading to topologically associating domain (TAD) formation in the interphase chromosome reproduces these behaviors. The phase diagram of this landscape shows the helical fiber order and the cylindrical shape persist at temperatures above the onset of chiral symmetry breaking which is limited by the TAD interaction strength.