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Review
. 2019 Jul;11(4):e1444.
doi: 10.1002/wsbm.1444. Epub 2018 Dec 19.

Models of polymer physics for the architecture of the cell nucleus

Andrea Esposito  1   2 , Carlo Annunziatella  1 , Simona Bianco  1 , Andrea M Chiariello  1 , Luca Fiorillo  1 , Mario Nicodemi  1   2   3
Affiliations
Review

Models of polymer physics for the architecture of the cell nucleus

Andrea Esposito et al. Wiley Interdiscip Rev Syst Biol Med. 2019 Jul.

Abstract

The depth and complexity of data now available on chromosome 3D architecture, derived by new technologies such as Hi-C, have triggered the development of models based on polymer physics to explain the observed patterns and the underlying molecular folding mechanisms. Here, we give an overview of some of the ideas and models from physics introduced to date, along with their progresses and limitations in the description of experimental data. In particular, we focus on the Strings&Binders and the Loop Extrusion model of chromatin architecture. This article is categorized under: Analytical and Computational Methods > Computational Methods.

Keywords: chromatin; computational biology; polymer physics.

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Conflict of interest statement

Conflict of interest

The authors declare no conflict of interest.

Figures

Figure 1.
Figure 1.. Schematic representation of polymer models describing chromatin folding.
a. The Strings&Binders Switch (SBS) model quantifies the biological scenario where diffusing transcription factors mediate DNA looping and folding. Its stable conformations can be derived by equilibrium thermodynamics. b. The Loop Extrusion (LE) model quantifies the off-equilibrium folding scenario where an active motor binds to DNA and actively extrude a DNA loop. c. The Slip-Link (SL) model is a variant without active, energy burning mechanisms, where DNA diffusively slips through a bridging factor.
Figure 2.
Figure 2.. Polymer models can reproduce Hi-C data.
a. The folding of the Sox9 locus in mESC is described by the SBS model with good accuracy: Hi-C (Dixon 2012) and model derived contact data have a Pearson correlation r=0.95. A single-molecule 3D conformation of the locus derived from the SBS is also shown to visualize the 3D structure corresponding to Hi-C patterns. Adapted from (Chiariello 2016). b. The LE model has been used to explain successfully the architecture of chromosomal loci where Cohesin/CTCF is the key driving force of folding, as the one in GM12878 cells shown in the example. Adapted from (Sanborn 2015).
Figure 3.
Figure 3.. Microphase separation and domain formation.
a. In the SBS view, stable architectural classes of polymer physics correspond to different thermodynamics phases. The SBS toy model with only one type of binders and binding sites, exhibits a coil-globule phase transition, where its 3D conformation switches from being open to compact. Adapted from (Chiariello 2016). b. In the SBS mixture model, the regions with red and green binding sites fold into distinct domains by microphase separation, as visible in the pairwise contact map. Adapted from (Barbieri 2012).
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