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. 2011 Apr 15:4:8.
doi: 10.1186/2046-1682-4-8.

Hierarchies in eukaryotic genome organization: Insights from polymer theory and simulations

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Hierarchies in eukaryotic genome organization: Insights from polymer theory and simulations

Balaji Vs Iyer et al. BMC Biophys. .

Abstract

Eukaryotic genomes possess an elaborate and dynamic higher-order structure within the limiting confines of the cell nucleus. Knowledge of the physical principles and the molecular machinery that govern the 3D organization of this structure and its regulation are key to understanding the relationship between genome structure and function. Elegant microscopy and chromosome conformation capture techniques supported by analysis based on polymer models are important steps in this direction. Here, we review results from these efforts and provide some additional insights that elucidate the relationship between structure and function at different hierarchical levels of genome organization.

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Figures

Figure 1
Figure 1
Illustration of the Genome Folding Problem. Illustration of the important question on genome organization. (Adapted with permission from cartoonist John Chase-http://www.chasetoons.com)
Figure 2
Figure 2
Hierarchies of Genome Organization. The hierarchical process by which eukaryotic double-stranded DNA (two meters long, in the case of humans) is packaged within the confines of a micrometers-sized cell. As shown schematically in the figure, this process encompasses three main organization levels classified as primary, secondary and tertiary [115,116].
Figure 3
Figure 3
Chromatin Modeling. Coarse grained models of 10 nm chromatin fiber with different level of details. (a) The simple two angle model has two parameters, the angles α and β [25]. (b) The detailed two angle model includes energy terms for stretching and bending of the bead-chain with an additional energy term for the relative twist angle between adjacent beads to account for the twisting rigidity of DNA [37]. (c) Representation of the detailed mesoscale model of Arya et al [44,45].
Figure 4
Figure 4
Nucleosome Depletion. Schematic of nucleosomal depletion associated persistence length modification and consequent local conformation change in the cell nucleus. formula image and formula image refer to the initial and final persistence length, respectively.
Figure 5
Figure 5
Loop Models. Illustration of the different loop models; (a) Random Loop model indicating loops at all scales > 150 kbp [90], (b) multi-loop subcompartment model with 120 kbp rosette structures [96] and (c) random-walk-giant-loop model with giant loops organized along a random backbone [75].
Figure 6
Figure 6
Random Loop and Fractal Globule. (a) Predictions of the random loop model for mean-square displacement (adapted from Mateos-Langerak et al [90]). (b) Predictions of the fractal globule model for probability of contact (adapted from the article of Lieberman-Aiden et al with permission from AAAS [91]).
Figure 7
Figure 7
Persistence Length Vs Folding Index. Plot illustrating persistence length as a function of folding index for ν = 1/3. The folding index is analogous to the resolution of a lens through which the genome is viewed and the persistence length corresponds to the length scale of observable correlations at this specific resolution.

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