Topology, structures, and energy landscapes of human chromosomes

Abstract

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 fibril-like 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.

Confinement-Induced Glassy Dynamics in a Model for Chromosome Organization

“…Such an interpretation of the structural organization based solely on P (s) is not universally accepted [9]. In addition, genome structure could vary depending on the extent of maturity of human cells [10]. Still, the scaling of P (s) varies depending on organisms.…”

Shape Transitions and Chiral Symmetry Breaking in the Energy Landscape of the Mitotic Chromosome

“…A complete understanding of chromosomal organization is challenging since the condensation of the chromosome into its dense mitotic form permits many different orderings and phase transitions. Owing to the large scale of the chromosome, we also can expect interesting non-equilibrium glassy dynamics and possible kinetic control of structure formation [5][6][7][8][9][10][11][12][13].Structural models of the mitotic chromosome have been proposed, including the radial loop model [4], the chromatin network model [14] and the hierarchical folding model [3]. These models often highlight the biologically specific role of protein molecules but the intrinsic properties of the DNA as a long highly helical molecule must also be at work.…”

“…A complete understanding of chromosomal organization is challenging since the condensation of the chromosome into its dense mitotic form permits many different orderings and phase transitions. Owing to the large scale of the chromosome, we also can expect interesting non-equilibrium glassy dynamics and possible kinetic control of structure formation [5][6][7][8][9][10][11][12][13].…”

“…The chiral twist collective variable probes structure at the 25 Mb scale. The fiber spectrum which we introduced in our previous study of the interphase chromosome gives evidence for structures at finer scales [5]. The fiber spectrum is the sequence Fourier transform of an orientation order parameter defined by the scalar product of two displacement vectors along the genomic sequence.…”

“…A hierarchically organized chromosome with liquid crystalline features and orientational ordering can arise from a generic ideal chromosome model [5]. An ideal chromosome potential represents an effective homopolymer with a pair-wise contact potential, whose strength depends only on the sequence separation of the two genomic loci, not on their specific locations.…”