Salt-Induced Conformation and Interaction Changes of Nucleosome Core Particles

Mangenot, Stéphanie; Leforestier, Amélie; Vachette, Patrice; Durand, Dominique; Livolant, Françoise

doi:10.1016/s0006-3495(02)75399-x

Cited by 117 publications

(165 citation statements)

References 45 publications

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“…In fact, we have tested different orientations of histone tails in our DiSCO model and found that the exact positions of the tails do not matter. The array stays in moderate folded forms at high salt as long as the tails protrude from nucleosome cores; the tails prefer protrusion at high salt as observed in experiments (62). Another approximation in the present model is our use of Debye-Hückel approximation, which accounts for neither the nonlinear effect from the polyelectrolyte feature of both the linker DNA and the nucleosomal DNA nor the contribution of desolvation terms.…”

Section: Discussionmentioning

confidence: 87%

Electrostatic mechanism of nucleosomal array folding revealed by computer simulation

Sun

Zhang

Schlick

2005

Proc. Natl. Acad. Sci. U.S.A.

110

113

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Although numerous experiments indicate that the chromatin fiber displays salt-dependent conformations, the associated molecular mechanism remains unclear. Here, we apply an irregular Discrete Surface Charge Optimization (DiSCO) model of the nucleosome with all histone tails incorporated to describe by Monte Carlo simulations salt-dependent rearrangements of a nucleosomal array with 12 nucleosomes. The ensemble of nucleosomal array conformations display salt-dependent condensation in good agreement with hydrodynamic measurements and suggest that the array adopts highly irregular 3D zig-zag conformations at high (physiological) salt concentrations and transitions into the extended ''beads-on-a-string'' conformation at low salt. Energy analyses indicate that the repulsion among linker DNA leads to this extended form, whereas internucleosome attraction drives the folding at high salt. The balance between these two contributions determines the salt-dependent condensation. Importantly, the internucleosome and linker DNA-nucleosome attractions require histone tails; we find that the H3 tails, in particular, are crucial for stabilizing the moderately folded fiber at physiological monovalent salt.chromatin modeling ͉ irregular 3D zig-zag ͉ Discrete Surface Charge Optimization model C hromatin folding and the dynamic interplay between chromatin structures and various cellular factors directly regulate fundamental gene expression and silencing processes (1-4). Extensive studies have probed the structural and dynamic properties of chromatin and the molecular mechanisms that determine these properties (5-8). Nonetheless, questions remain concerning how a chain of nucleosomes connected by linker DNA folds into a condensed 30-nm chromatin fiber under physiological conditions (9) and what the exact arrangements of nucleosomes in the 30-nm fiber are (6). Two principal architectures of fiber arrangement proposed are the solenoid and zig-zag models. They differ significantly in how the linker DNA is arranged within the condensed chromatin fiber. In the solenoid model, the linker DNA is bent such that the consecutive nucleosomes interact with each other and form a helix (10-14); in the zig-zag model, the linker DNA remains straight and crosses the fiber axis so that the consecutive nucleosomes appear at the opposite side of the fiber axis (5, 15-18).The structure of chromatin strongly depends on the salt environment, both in terms of the valence of the ions and their concentration in solution (1). At low salt concentrations, chromatin adopts the extended ''beads-on-a-string'' conformation, whereas at high salt concentrations it folds into compact forms. In the presence of linker histones (H1 or H5) under physiological salt conditions, chromatin forms the folded 30-nm fiber. The histone tails are known to be crucial for the folding of chromatin fibers (19-21; reviewed in ref. 22). The tail domains, accounting for Ϸ50% of the positive charges of the histone octamer, are located at the N-terminal portions of H2A, H2B, H3, and H4, and ...

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Section: Discussionmentioning

confidence: 87%

Electrostatic mechanism of nucleosomal array folding revealed by computer simulation

Sun

Zhang

Schlick

2005

Proc. Natl. Acad. Sci. U.S.A.

110

113

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“…6,7,16,20 Although the distribution of DNA chain segments in DNA brushes has not been fully resolved, 16,17 we here use the Alexander approximation, which assumes that the local concentration of Kuhn segments is uniform in the brush region. 21 This treatment highlights the roles played by transcription for chromatin structures, rather than the details of brush models.…”

Section: Modelmentioning

confidence: 99%

Transcription Driven Phase Separation in Chromatin Brush

Yamamoto

Schiessel

2016

Langmuir

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We theoretically predict the local density of nucleosomes on DNA brushes in a solution of molecules, which are necessary for transcription and the assembly of nucleosomes. Our theory predicts that in a confined space, DNA brushes show phase separation, where a region of relatively large nucleosomal occupancy coexists with a region of smaller nucleosomal occupancy. This phase separation is driven by an instability arising from the fact that the rate of transcription increases as the nucleosomal occupancy decreases due to the excluded volume interactions between nucleosomes and RNA polymerase during thermal diffusion and, in turn, nucleosomes are (in some cases) desorbed from DNA when RNA polymerase collides with nucleosomes during transcription. The miscibility phase diagram shows critical points, which are sensitive to the rate constants involved in transcription, the changes of interactions of DNA chain segments by assembling nucleosomes, and pressures that are applied to the brushes. INTRODUCTIONThe DNA of eukaryotic cells is folded into compact chromatin structures to fit the size of their nuclei.1 The repeating unit of chromatin is the nucleosome, where DNA is wrapped around an octamer of histone proteins, in some cases guided by chaperons. The first step to express genetic information that is encoded in the sequence of nucleotides along DNA is transcription, by which the complementary sequence of RNA is synthesized by enzymes called RNA polymerase (RNAP). The rate of transcription of each gene decreases as the local packing density of nucleosomes at the corresponding sequence of DNA increases.Recent experiments have shown that chromatin of embryonic stem (ES) cells displays fluctuations of the local nucleosome concentration over relatively long time (∼ min) and length scales (∼ μm), analogous to critical fluctuations.2 In contrast, differentiated cells show more static structures, where regions of relatively large local concentrations of nucleosomes (heterochromatin) coexist with regions of relatively low local concentrations of nucleosomes (euchromatin), analogous to two-phase coexistent states. Because the transcription rate of each gene depends on the local concentrations of nucleosomes along the corresponding DNA stretch, the critical fluctuations of chromatin structures may play an important role in maintaining the pluripotency of ES cells. Moreover, the processes of phase separation during differentiation may be relevant to the lineage determination.In the usual case of phase separation, critical fluctuations are driven by attractive interactions between molecules and random forces.3 Nucleosomes (which have net negative charges) show attractive interactions via histone tails (which

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“…For instance, close 345 The presence of 8 highly basic Arg/Lys-rich flexible N-terminal histone tails was associated with the NCP aggregation via ''tail-bridging'' effect in some experiments, 346 computer simulations, [347][348][349] and theoretical models. 310,350 Tails-mediated NCP-NCP attraction, 351 present at elevated [salt] only, seems however to be not very specific with respect to mutual NCP-NCP orientations and as such is not likely to generate highlystructured chromatin fibers. Conversely, the close-range DNA-mediated ES side-to-side NCP-NCP contacts might be capable of doing so.…”

Section: B Dense Phases Of Ncpsmentioning

confidence: 99%

Electrostatic interactions in biological DNA-related systems

Cherstvy

2011

Phys. Chem. Chem. Phys.

163

148

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In this perspective article, we focus on recent developments in the theory of charge effects in biological DNA-related systems. The electrostatic effects on different levels of DNA organization are considered, including the DNA-DNA interactions, DNA complexation with cationic lipid membranes, DNA condensates and DNA-dense cholesteric phases, protein-DNA recognition, DNA wrapping in nucleosomes, and inter-nucleosomal interactions. For these systems, we develop a theoretical framework to describe the physical-chemical mechanisms of structure formation and anticipate some biological consequences. General biophysical principles of DNA compaction in chromatin fibers and DNA spooling inside viral capsids are discussed in the end, with emphasis on electrostatic aspects.

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Salt-Induced Conformation and Interaction Changes of Nucleosome Core Particles

Cited by 117 publications

References 45 publications

Electrostatic mechanism of nucleosomal array folding revealed by computer simulation

Electrostatic mechanism of nucleosomal array folding revealed by computer simulation

Transcription Driven Phase Separation in Chromatin Brush

Electrostatic interactions in biological DNA-related systems

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