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Article Dans Une Revue PLoS Computational Biology Année : 2015

Differential Chromosome Conformations as Hallmarks of Cellular Identity Revealed by Mathematical Polymer Modeling

Résumé

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. yeast chromosome 3 is mating type specific in G1. Differential folding of the left arm of this chromosome can be attributed to a small DNA element which could explain why loci on this arm may be excluded from recombination with the MAT locus on the right arm of chromosome 3. Chromatin structural properties altered in the absence of the Asf1 histone chaperone contribute to the lineage specific chromosome organization and the relative position of the three mating type loci.
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Dates et versions

hal-03026206 , version 1 (03-12-2020)

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Imen Lassadi, Alain Kamgoué, Isabelle Goiffon, Nicolas Tanguy-Le-Gac, Kerstin Bystricky. Differential Chromosome Conformations as Hallmarks of Cellular Identity Revealed by Mathematical Polymer Modeling. PLoS Computational Biology, 2015, 11 (6), pp.e1004306. ⟨10.1371/journal.pcbi.1004306⟩. ⟨hal-03026206⟩
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