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

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 105 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.\n\nAuthor SummaryA key determining factor in many important cellular processes as DNA transcription, for instance, the specific composition of the chromatin fiber sequence has a major influence on chromosome folding during interphase. Yet, how this is achieved in detail remains largely elusive. In this work, we explore this link by means of a novel quantitative computational polymer model for interphase chromosomes where the associated chromatin filaments are composed of mixtures of fibers with heterogeneous physical properties. Our work suggests a scenario where chromosomes undergo only limited reorganization, namely on length-scales below 105 basepairs and time-scales shorter than a few seconds. Our conclusions are supported by recent FISH data on murine chromosomes.