Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 112, Issue 19, Pages 6062-6067Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1506257112
Keywords
chromosome conformation capture; maximum entropy; topologically associating domains; liquid crystal
Categories
Funding
- Center for Theoretical Biological Physics
- National Science Foundation [PHY-1308264, PHY-1427654]
- D. R. Bullard-Welch Chair at Rice University Grant [C-0016]
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Chromosome conformation capture experiments provide a rich set of data concerning the spatial organization of the genome. We use these data along with a maximum entropy approach to derive a least-biased effective energy landscape for the chromosome. Simulations of the ensemble of chromosome conformations based on the resulting information theoretic landscape not only accurately reproduce experimental contact probabilities, but also provide a picture of chromosome dynamics and topology. The topology of the simulated chromosomes is probed by computing the distribution of their knot invariants. The simulated chromosome structures are largely free of knots. Topologically associating domains are shown to be crucial for establishing these knotless structures. The simulated chromosome conformations exhibit a tendency to form fibrillike structures like those observed via light microscopy. The topologically associating domains of the interphase chromosome exhibit multistability with varying liquid crystalline ordering that may allow discrete unfolding events and the landscape is locally funneled toward ideal chromosome structures that represent hierarchical fibrils of fibrils.
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