Large Scale Chromosome Folding Is Stable against Local Changes in Chromatin Structure.

Ana-Maria Florescu,Angelo Rosa,Pierre Therizols

doi:10.1371/journal.pcbi.1004987

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.

Highlights

Understanding how genomes fold within the crowded environment of the nucleus [1] during interphase represents a necessary step for the comprehension of important cellular processes such as gene expression and regulation [2]
A 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
How this is achieved in detail remains largely elusive. 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

Summary

Introduction

Understanding how genomes fold within the crowded environment of the nucleus [1] during interphase represents a necessary step for the comprehension of important cellular processes such as gene expression and regulation [2]. In in vitro conditions close to the physiological ones, this fiber is observed to fold into a thicker, more compact structure known as the 30nm fiber [1], whose role and existence in vivo are still quite debated [9, 10]. Chromosome loci within TADs interact frequently between themselves, but less frequently across different TADs. chromosomes do not spread inside the whole nucleus, rather they occupy well localized nuclear regions (the so-called “chromosome territories”) which play a crucial role in gene expression and regulation [11]

Methods

Results

Discussion

Conclusion