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Torsional behavior of chromatin is modulated by rotational phasing of nucleosomes.

Nam GM, Arya G - Nucleic Acids Res. (2014)

Bottom Line: Torsionally stressed DNA plays a critical role in genome organization and regulation.While the effects of torsional stresses on naked DNA have been well studied, little is known about how these stresses propagate within chromatin and affect its organization.The observed behavior is shown to arise from an interplay between nucleosomal transitions into states with crossed and open linker DNAs and global supercoiling of arrays into left- and right-handed coils, where Ψ0 serves to modulate the energy landscape of nucleosomal states.

View Article: PubMed Central - PubMed

Affiliation: Department of NanoEngineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0448, USA.

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Rotational phase angle of nucleosomes and simulation setup. (a-c) Length and helical pitch of linker DNAs determines nucleosome phasing, and affects nucleosome topology: (b) l < nbp (where nb is an integer, equal to 6 in this study) leads to counter-clockwise rotation of downstream nucleosome 2 with respect to upstream nucleosome 1 (Ψ0 < 0) leading to more open linker DNAs; (b) l = nbp leads to in-phase nucleosomes (Ψ0 = 0); and (c) l > nbp leads to clockwise rotation of 2 with respect to 1 (Ψ0 > 0) leading to more crossed linker DNAs. (d) Simulation setup for studying the torsional response of nucleosome arrays. External twisting Ω is applied by rotating the last linker DNA frame by angle ΔΩ in a step-wise manner every Δteq while being subjected to a stretching force F. The repulsive line potential is drawn as dotted line and the DNAs and histone core are shown in red and gray, respectively.
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Figure 1: Rotational phase angle of nucleosomes and simulation setup. (a-c) Length and helical pitch of linker DNAs determines nucleosome phasing, and affects nucleosome topology: (b) l < nbp (where nb is an integer, equal to 6 in this study) leads to counter-clockwise rotation of downstream nucleosome 2 with respect to upstream nucleosome 1 (Ψ0 < 0) leading to more open linker DNAs; (b) l = nbp leads to in-phase nucleosomes (Ψ0 = 0); and (c) l > nbp leads to clockwise rotation of 2 with respect to 1 (Ψ0 > 0) leading to more crossed linker DNAs. (d) Simulation setup for studying the torsional response of nucleosome arrays. External twisting Ω is applied by rotating the last linker DNA frame by angle ΔΩ in a step-wise manner every Δteq while being subjected to a stretching force F. The repulsive line potential is drawn as dotted line and the DNAs and histone core are shown in red and gray, respectively.

Mentions: Here, we provide the first detailed picture of the structure and dynamics of supercoiled nucleosome arrays through Brownian dynamics (BD) simulations of a coarse-grained (CG) model of nucleosome arrays that we have developed and validated against multiple types of experiments (26–28). The model captures the essential physics of chromatin folding, including the bending and twisting mechanics of linker DNAs, the excluded volume and DNA entry/exit geometry of nucleosomes, and the electrostatics of nucleosomes and linker DNAs. The BD simulations account for thermal fluctuations and viscous drag from solvent while computing the dynamics of each array component in the model. This approach allows us to obtain both the Boltzmann-distributed ensemble of array conformations at varying degrees of supercoiling and the real-time dynamics of DNA twist propagation along the arrays. To demonstrate how the intrinsic topology of arrays dictates their torsional behavior, we examine the effects of the phase angle Ψ0 defined as the intrinsic rotational angle between adjacent nucleosomes when the intervening linker DNAs are completely relaxed (undeformed) (29,30). As shown in Figure 1a–c, Ψ0 is determined by the ratio of the length l and average helical pitch p of the linker DNA, and it directly affects the nucleosomal entry/exit configuration of the linker DNAs, which in turn modulates the internal writhe of each nucleosome and the global structure of the arrays (31,32).


Torsional behavior of chromatin is modulated by rotational phasing of nucleosomes.

Nam GM, Arya G - Nucleic Acids Res. (2014)

Rotational phase angle of nucleosomes and simulation setup. (a-c) Length and helical pitch of linker DNAs determines nucleosome phasing, and affects nucleosome topology: (b) l < nbp (where nb is an integer, equal to 6 in this study) leads to counter-clockwise rotation of downstream nucleosome 2 with respect to upstream nucleosome 1 (Ψ0 < 0) leading to more open linker DNAs; (b) l = nbp leads to in-phase nucleosomes (Ψ0 = 0); and (c) l > nbp leads to clockwise rotation of 2 with respect to 1 (Ψ0 > 0) leading to more crossed linker DNAs. (d) Simulation setup for studying the torsional response of nucleosome arrays. External twisting Ω is applied by rotating the last linker DNA frame by angle ΔΩ in a step-wise manner every Δteq while being subjected to a stretching force F. The repulsive line potential is drawn as dotted line and the DNAs and histone core are shown in red and gray, respectively.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4150795&req=5

Figure 1: Rotational phase angle of nucleosomes and simulation setup. (a-c) Length and helical pitch of linker DNAs determines nucleosome phasing, and affects nucleosome topology: (b) l < nbp (where nb is an integer, equal to 6 in this study) leads to counter-clockwise rotation of downstream nucleosome 2 with respect to upstream nucleosome 1 (Ψ0 < 0) leading to more open linker DNAs; (b) l = nbp leads to in-phase nucleosomes (Ψ0 = 0); and (c) l > nbp leads to clockwise rotation of 2 with respect to 1 (Ψ0 > 0) leading to more crossed linker DNAs. (d) Simulation setup for studying the torsional response of nucleosome arrays. External twisting Ω is applied by rotating the last linker DNA frame by angle ΔΩ in a step-wise manner every Δteq while being subjected to a stretching force F. The repulsive line potential is drawn as dotted line and the DNAs and histone core are shown in red and gray, respectively.
Mentions: Here, we provide the first detailed picture of the structure and dynamics of supercoiled nucleosome arrays through Brownian dynamics (BD) simulations of a coarse-grained (CG) model of nucleosome arrays that we have developed and validated against multiple types of experiments (26–28). The model captures the essential physics of chromatin folding, including the bending and twisting mechanics of linker DNAs, the excluded volume and DNA entry/exit geometry of nucleosomes, and the electrostatics of nucleosomes and linker DNAs. The BD simulations account for thermal fluctuations and viscous drag from solvent while computing the dynamics of each array component in the model. This approach allows us to obtain both the Boltzmann-distributed ensemble of array conformations at varying degrees of supercoiling and the real-time dynamics of DNA twist propagation along the arrays. To demonstrate how the intrinsic topology of arrays dictates their torsional behavior, we examine the effects of the phase angle Ψ0 defined as the intrinsic rotational angle between adjacent nucleosomes when the intervening linker DNAs are completely relaxed (undeformed) (29,30). As shown in Figure 1a–c, Ψ0 is determined by the ratio of the length l and average helical pitch p of the linker DNA, and it directly affects the nucleosomal entry/exit configuration of the linker DNAs, which in turn modulates the internal writhe of each nucleosome and the global structure of the arrays (31,32).

Bottom Line: Torsionally stressed DNA plays a critical role in genome organization and regulation.While the effects of torsional stresses on naked DNA have been well studied, little is known about how these stresses propagate within chromatin and affect its organization.The observed behavior is shown to arise from an interplay between nucleosomal transitions into states with crossed and open linker DNAs and global supercoiling of arrays into left- and right-handed coils, where Ψ0 serves to modulate the energy landscape of nucleosomal states.

View Article: PubMed Central - PubMed

Affiliation: Department of NanoEngineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0448, USA.

Show MeSH
Related in: MedlinePlus