Footprints of loop extrusion in statistics of intra-chromosomal distances: an analytically solvable model

TL;DR

This paper presents an analytically solvable polymer model to understand how active loop extrusion influences the statistical distribution of distances between genomic loci, providing insights into chromatin organization.

Contribution

It introduces a simple, analytically solvable model of interphase chromosomes with sparse loops, extending beyond the one-loop approximation and analyzing deviations from Gaussian statistics.

Findings

Derived a closed-form expression for mean-squared distances between loci.

Analyzed how loops cause deviations from Gaussian chain behavior.

Suggested methods to estimate loop extrusion characteristics from experimental data.

Abstract

Active loop extrusion - the process of formation of dynamically growing chromatin loops due to the motor activity of DNA-binding protein complexes - is firmly established mechanism responsible for chromatin spatial organization at different stages of cell cycle in eukaryotes and bacteria. The theoretical insight into the effect of loop extrusion on the experimentally measured statistics of chromatin conformation can be gained with an appropriately chosen polymer model. Here we consider the simplest analytically solvable model of interphase chromosome which is treated as ideal chain with disorder of sufficiently sparse random loops whose conformations are sampled from the equilibrium ensemble. This framework allows us to arrive at the closed-form analytical expression for the mean-squared distance between pairs of genomic loci which is valid beyond the one-loop approximation in diagrammatic representation. Besides, we analyse the loops-induced deviation of chain conformations from the Gaussian statistics by calculating kurtosis of probability density of the pairwise separation vector. The presented results suggest the possible ways of estimating the characteristics of the loop extrusion process based on the experimental data on the scale-dependent statistics of intra-chromosomal pair-wise distances.