Differential chromosome conformations as hallmarks of cellular identity revealed by mathematical polymer modeling

PLoS Comput Biol. 2015 Jun 1;11(6):e1004306. doi: 10.1371/journal.pcbi.1004306. eCollection 2015 Jun.

Abstract

Inherently dynamic, chromosomes adopt many different conformations in response to DNA metabolism. Models of chromosome organization in the yeast nucleus obtained from genome-wide chromosome conformation data or biophysical simulations provide important insights into the average behavior but fail to reveal features from dynamic or transient events that are only visible in a fraction of cells at any given moment. We developed a method to determine chromosome conformation from relative positions of three fluorescently tagged DNA in living cells imaged in 3D. Cell type specific chromosome folding properties could be assigned based on positional combinations between three loci on yeast chromosome 3. We determined that the shorter left arm of chromosome 3 is extended in MATα cells, but can be crumpled in MATa cells. Furthermore, we implemented a new mathematical model that provides for the first time an estimate of the relative physical constraint of three linked loci related to cellular identity. Variations in this estimate allowed us to predict functional consequences from chromatin structural alterations in asf1 and recombination enhancer deletion mutant cells. The computational method is applicable to identify and characterize dynamic chromosome conformations in any cell type.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosome Structures / chemistry*
  • Chromosome Structures / ultrastructure*
  • Chromosomes, Fungal / chemistry*
  • Chromosomes, Fungal / ultrastructure*
  • Computational Biology
  • Computer Simulation
  • Genetic Loci
  • Models, Genetic*
  • Molecular Conformation
  • Saccharomyces cerevisiae / ultrastructure*

Associated data

  • Dryad/10.5061/dryad.RP3G3

Grant support

Financial support was provided by the Institut Universitaire de France (IUF), the Agence Nationale de le Recherche (ANR) and a HFSPO research grant RGP0044, The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.