A estabilidade em larga escala dos cromossomos

quinta-feira, junho 30, 2016

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

Ana-Maria Florescu , Pierre Therizols, Angelo Rosa 


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.

Author Summary

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. 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.

Citation: Florescu A-M, Therizols P, Rosa A (2016) Large Scale Chromosome Folding Is Stable against Local Changes in Chromatin Structure. PLoS Comput Biol 12(6): e1004987. doi:10.1371/journal.pcbi.1004987

Editor: Marc A. Marti-Renom, CNAG - Centre Nacional d’Anàlisi Genòmica and CRG - Centre de Regulació Genòmica, SPAIN

Received: November 5, 2015; Accepted: May 17, 2016; Published: June 13, 2016

Copyright: © 2016 Florescu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the paper and its Supporting Information files.

Funding: AR has received financing from Italian Ministry of Research through project PRIN - 2010 HXAW77 (http://prin.miur.it/). PT has recieved financing from Agence Nationale de la Recherche through grant IDEX-SLI (DXCAIHUSLI-EF14). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

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