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A predictive computational model of the dynamic 3D interphase yeast nucleus.

By Hua Wong, Hervé Marie-Nelly, Sébastien Herbert, Pascal Carrivain, Hervé Blanc, Romain Koszul, Emmanuelle Fabre and Christophe Zimmer

Abstract

International audienceBackgroundDespite the absence of internal membranes, the nucleus of eukaryotic cells is spatially organized, with chromosomes and individual loci occupying dynamic, but nonrandom, spatial positions relative to nuclear landmarks and to each other. These positional preferences correlate with gene expression and DNA repair, recombination, and replication. Yet the principles that govern nuclear organization remain poorly understood and detailed predictive models are lacking.ResultsWe present a computational model of dynamic chromosome configurations in the interphase yeast nucleus that is based on first principles and is able to statistically predict the positioning of any locus in nuclear space. Despite its simplicity, the model agrees with extensive previous and new measurements on locus positioning and with genome-wide DNA contact frequencies. Notably, our model recapitulates the position and morphology of the nucleolus, the observed variations in locus positions, and variations in contact frequencies within and across chromosomes, as well as subchromosomal contact features. The model is also able to correctly predict nuclear reorganization accompanying a reduction in ribosomal DNA transcription, and sites of chromosomal rearrangements tend to occur where the model predicted high contact frequencies.ConclusionsOur results suggest that large-scale yeast nuclear architecture can be largely understood as a consequence of generic properties of crowded polymers rather than of specific DNA-binding factors and that configurations of chromosomes and DNA contacts are dictated mainly by genomic location and chromosome lengths. Our model provides a quantitative framework to understand and predict large-scale spatial genome organization and its interplay with functional processes

Topics: MESH : Cell Nucleus/genetics, MESH : Cell Nucleus/physiology, MESH : Sequence Analysis, DNA, MESH : Transcription, Genetic, MESH : Cell Nucleus/ultrastructure, MESH : Chromatin, MESH : Chromosomes, Fungal, MESH : Computational Biology/methods, MESH : Computer Simulation, MESH : DNA Replication, MESH : Interphase, MESH : Nucleolus Organizer Region/physiology, MESH : Saccharomyces cerevisiae/genetics, MESH : Saccharomyces cerevisiae/physiology, MESH : Saccharomyces cerevisiae/ultrastructure, [ SDV.GEN ] Life Sciences [q-bio]/Genetics
Publisher: Elsevier
Year: 2012
DOI identifier: 10.1016/j.cub.2012.07.069
OAI identifier: oai:HAL:pasteur-01420017v1
Provided by: Hal-Diderot
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