Modelling chromatin structure and dynamics: status and prospects

Korolev, Nikolay; Fan, Yanping; Lyubartsev, Alexander P.; Nordenskiöld, Lars

doi:10.1016/j.sbi.2012.01.006

Cited by 39 publications

(42 citation statements)

References 70 publications

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“…Our model should represent an important step towards modeling of DNA bending properties in CG multi-scale modeling of a chromatin fiber, for which the description of the stiffness of linker DNA is highly important in order to reproduce chromatin folding induced by multivalent cations [81]. It may also be noted that, although the present approach is based on a CG DNA model without base sequence identity, this can be introduced in a rather straightforward way by assigning different types of D beads for variable two-bp sequence units.…”

Section: Discussionmentioning

confidence: 99%

A Coarse-Grained DNA Model Parameterized from Atomistic Simulations by Inverse Monte Carlo

et al. 2014

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Abstract:Computer modeling of very large biomolecular systems, such as long DNA polyelectrolytes or protein-DNA complex-like chromatin cannot reach all-atom resolution in a foreseeable future and this necessitates the development of coarse-grained (CG) approximations. DNA is both highly charged and mechanically rigid semi-flexible polymer and adequate DNA modeling requires a correct description of both its structural stiffness and salt-dependent electrostatic forces. Here, we present a novel CG model of DNA that approximates the DNA polymer as a chain of 5-bead units. Each unit represents two DNA base pairs with one central bead for bases and pentose moieties and four others for phosphate groups. Charges, intra-and inter-molecular force field potentials for the CG DNA model were calculated using the inverse Monte Carlo method from all atom molecular dynamic (MD) simulations of 22 bp DNA oligonucleotides. The CG model was tested by performing dielectric continuum Langevin MD simulations of a 200 bp double helix DNA in solutions of monovalent salt with explicit ions. Excellent agreement with experimental data was obtained for the dependence of the DNA persistent length on salt concentration in the range 0.1-100 mM. The new CG DNA model is suitable for modeling various biomolecular systems with adequate description of electrostatic and mechanical properties.

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Section: Discussionmentioning

confidence: 99%

A Coarse-Grained DNA Model Parameterized from Atomistic Simulations by Inverse Monte Carlo

et al. 2014

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“…A number of experimental [30][31][32][33], theoretical [34][35][36], and computer simulation studies [37][38][39][40][41][42][43][44][45] have emerged on this subject in recent years. Chromatin 30-nm fibers interact electrostatically with each other via "contacting" NCPs positioned on the fiber periphery, both in canonical solenoidal [46,47] and crosslinked [34] fiber models.…”

Section: Interactions Between the Chromatin Fibersmentioning

confidence: 99%

Structure-driven homology pairing of chromatin fibers: the role of electrostatics and protein-induced bridging

Cherstvy

Teif

2013

J Biol Phys

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Chromatin domains formed in vivo are characterized by different types of 3D organization of interconnected nucleosomes and architectural proteins. Here, we quantitatively test a hypothesis that the similarities in the structure of chromatin fibers (which we call "structural homology") can affect their mutual electrostatic and protein-mediated bridging interactions. For example, highly repetitive DNA sequences in heterochromatic regions can position nucleosomes so that preferred inter-nucleosomal distances are preserved on the surfaces of neighboring fibers. On the contrary, the segments of chromatin fiber formed on unrelated DNA sequences have different geometrical parameters and lack structural complementarity pivotal for stable association and cohesion. Furthermore, specific functional elements such as insulator regions, transcription start and termination sites, and replication origins are characterized by strong nucleosome ordering that might induce structure-driven iterations of chromatin fibers. We propose that shape-specific protein-bridging interactions facilitate long-range pairing of chromatin fragments, while for closely-juxtaposed fibers electrostatic forces can in addition yield fine-tuned structurespecific recognition and pairing. These pairing effects can account for some features observed for mitotic and inter-phase chromatins.

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“…In recent years, approaches to model chromatin structure and dynamics by means of computer simulation considering the effects of energy and thermal fluctuations have made significant progress as reviewed recently (26). In particular, the size of systems and level of molecular detail amenable to numerical simulations has been largely improved (30)(31)(32). Current models of the 30 nm chromatin fiber frequently assume regularly spaced nucleosomes with uniform linker DNA length.…”

Section: Introductionmentioning

confidence: 99%

Changing Chromatin Fiber Conformation by Nucleosome Repositioning

Müller

Kepper

Schöpflin

et al. 2014

Biophysical Journal

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Chromatin conformation is dynamic and heterogeneous with respect to nucleosome positions, which can be changed by chromatin remodeling complexes in the cell. These molecular machines hydrolyze ATP to translocate or evict nucleosomes, and establish loci with regularly and more irregularly spaced nucleosomes as well as nucleosome-depleted regions. The impact of nucleosome repositioning on the three-dimensional chromatin structure is only poorly understood. Here, we address this issue by using a coarse-grained computer model of arrays of 101 nucleosomes considering several chromatin fiber models with and without linker histones, respectively. We investigated the folding of the chain in dependence of the position of the central nucleosome by changing the length of the adjacent linker DNA in basepair steps. We found in our simulations that these translocations had a strong effect on the shape and properties of chromatin fibers: i), Fiber curvature and flexibility at the center were largely increased and long-range contacts between distant nucleosomes on the chain were promoted. ii), The highest destabilization of the fiber conformation occurred for a nucleosome shifted by two basepairs from regular spacing, whereas effects of linker DNA changes of ?10 bp in phase with the helical twist of DNA were minimal. iii), A fiber conformation can stabilize a regular spacing of nucleosomes inasmuch as favorable stacking interactions between nucleosomes are facilitated. This can oppose nucleosome translocations and increase the energetic costs for chromatin remodeling. Our computational modeling framework makes it possible to describe the conformational heterogeneity of chromatin in terms of nucleosome positions, and thus advances theoretical models toward a better understanding of how genome compaction and access are regulated within the cell.

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Modelling chromatin structure and dynamics: status and prospects

Cited by 39 publications

References 70 publications

A Coarse-Grained DNA Model Parameterized from Atomistic Simulations by Inverse Monte Carlo

A Coarse-Grained DNA Model Parameterized from Atomistic Simulations by Inverse Monte Carlo

Structure-driven homology pairing of chromatin fibers: the role of electrostatics and protein-induced bridging

Changing Chromatin Fiber Conformation by Nucleosome Repositioning

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