A Polymer Physics View on Universal and Sequence-Specific Aspects of Chromosome Folding

Jost, Daniel; Rosa, Angelo; Vaillant, Cédric; Everaers, Ralf

doi:10.1016/b978-0-12-803480-4.00006-5

Cited by 12 publications

(16 citation statements)

References 108 publications

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“…During interphase chromosomes display several universal properties, e.g., scale free nature in subchain extension [58], and average contact probabilities [45] similar to homopolymers but with exponents that differ from simple chains [59,60]. At small separations the chromosomal architecture is determined by its bending rigidity, while at long range they show behavior typical of fractal globules [45,[61][62][63][64][65][66]. The contact maps reveal topologically associated domains at smaller genomic separations ( 1 Mbp) [12,67], and cell type specific checkerboard patterns at larger scales [45].…”

Section: Introductionmentioning

confidence: 99%

Cross-linker mediated compaction and local morphologies in a model chromosome

Kumar

Chaudhuri

2019

J. Phys.: Condens. Matter

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Chromatin and associated proteins constitute the highly folded structure of chromosomes. We consider a self-avoiding polymer model of the chromatin, segments of which may get cross-linked via protein binders that repel each other. The binders cluster together via the polymer mediated attraction, in turn, folding the polymer. Using molecular dynamics simulations, and a mean field description, we explicitly demonstrate the continuous nature of the folding transition, characterized by unimodal distributions of the polymer size across the transition. At the transition point the chromatin size and cross-linker clusters display large fluctuations, and a maximum in their negative cross-correlation, apart from a critical slowing down. Along the transition, we distinguish the local chain morphologies in terms of topological loops, inter-loop gaps, and zippering. The topologies are dominated by simply connected loops at the criticality, and by zippering in the folded phase. arXiv:1811.08172v2 [cond-mat.soft]

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Section: Introductionmentioning

confidence: 99%

Cross-linker mediated compaction and local morphologies in a model chromosome

Kumar

Chaudhuri

2019

J. Phys.: Condens. Matter

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“…An important open question regards the extent to which these active mechanisms are involved in the shaping the overall intra- and inter-chromosome architecture. This point, we believe, can be significantly advanced in future studies with a tight synergy of experiments and models (Goloborodko et al, 2016; Jost et al, 2017; Valdés et al, 2019).…”

Section: Discussionmentioning

confidence: 87%

“…The interpretation of these experimental results has been aided by an intense theoretical and computational activity that demonstrated how salient genomic architecture properties can be reproduced by a broad range of polymer models, and hence are likely governed by general physical mechanisms (Mirny, 2011; Rosa and Zimmer, 2014; Bianco et al, 2017; Haddad et al, 2017; Jost et al, 2017; Tiana and Giorgetti, 2018). This applies in particular to the aforementioned properties (i–iv) which can be rationalized as manifestations of the topological constraints that rule the behavior of semi-dilute or dense polymer systems, particularly their relaxation time scales (Doi and Edwards, 1986).…”

Section: Intra- and Inter-chromosome Architecturementioning

confidence: 99%

Topological Constraints in Eukaryotic Genomes and How They Can Be Exploited to Improve Spatial Models of Chromosomes

Rosa

Stefano

Micheletti

2019

Front. Mol. Biosci.

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Several orders of magnitude typically separate the contour length of eukaryotic chromosomes and the size of the nucleus where they are confined. The ensuing topological constraints can slow down the relaxation dynamics of genomic filaments to the point that mammalian chromosomes are never in equilibrium over a cell's lifetime. In this opinion article, we revisit these out-of-equilibrium effects and discuss how their inclusion in physical models can enhance the spatial reconstructions of interphase eukaryotic genomes from phenomenological constraints collected during interphase.

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“…capture the full complexity of genome organization, however. 42 We added the following modifications to better describe inter-chromosomal interactions. First, we defined a new type C to recognize centromeric regions and distinguish them from the A/B compartments.…”

Section: A Data-driven Mechanistic Model For the Diploid Human Genomementioning

confidence: 99%

Data-Driven Polymer Model for Mechanistic Exploration of Diploid Genome Organization

Reyes

Johnstone

et al. 2020

Biophysical Journal

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Chromosomes are positioned non-randomly inside the nucleus to coordinate with their transcriptional activity. The molecular mechanisms that dictate the global genome organization and the nuclear localization of individual chromosomes are not fully understood. We introduce a polymer model to study the organization of the diploid human genome: it is data-driven as all parameters can be derived from Hi-C data; it is also a mechanistic model since the energy function is explicitly written out based on a few biologically motivated hypotheses. These two features distinguish the model from existing approaches and make it useful both for reconstructing genome structures and for exploring the principles of genome organization. We carried out extensive validations to show that simulated genome structures reproduce a wide variety of experimental measurements, including chromosome radial positions and spatial distances between homologous pairs. Detailed mechanistic investigations support the importance of both specific inter-chromosomal interactions and centromere clustering for chromosome positioning. We anticipate the polymer model, when combined with Hi-C experiments, to be a powerful tool for investigating large scale rearrangements in genome structure upon cell differentiation and tumor progression. 2.

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A Polymer Physics View on Universal and Sequence-Specific Aspects of Chromosome Folding

Cited by 12 publications

References 108 publications

Cross-linker mediated compaction and local morphologies in a model chromosome

Cross-linker mediated compaction and local morphologies in a model chromosome

Topological Constraints in Eukaryotic Genomes and How They Can Be Exploited to Improve Spatial Models of Chromosomes

Data-Driven Polymer Model for Mechanistic Exploration of Diploid Genome Organization

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