Large scale chromosome folding is stable against local changes in chromatin structure

TL;DR

This study presents a biophysical model showing that large-scale chromosome folding remains stable despite local chromatin structure changes, with significant conformational shifts occurring only at smaller scales and shorter times.

Contribution

The paper introduces a simple biophysical model linking small-scale chromatin variations to large-scale chromosome stability, validated by experimental data.

Findings

Chromosomes show stability at large scales despite local changes.

Conformational changes are limited to scales smaller than 10^5 basepairs.

Detection of chromosome reorganization is constrained to short time and length scales.

Abstract

Characterizing the link between small-scale chromatin structure and large-scale chromosome folding during interphase is a prerequisite for understanding transcription. Yet, this link remains poorly investigated. Here, we introduce a simple biophysical model where interphase chromosomes are described in terms of the folding of chromatin sequences composed of alternating blocks of fibers with different thicknesses and flexibilities, and we use it to study the influence of sequence disorder on chromosome behaviors in space and time. By employing extensive computer simulations,we thus demonstrate that chromosomes undergo noticeable conformational changes only on length-scales smaller than $10^5$ basepairs and time-scales shorter than a few seconds, and we suggest there might exist effective upper bounds to the detection of chromosome reorganization in eukaryotes. We prove the relevance of our framework by modeling recent experimental FISH data on murine chromosomes.