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

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. Here we investigate the torsional behavior of nucleosome arrays by means of Brownian dynamics simulations of a coarse-grained model of chromatin. Our simulations reveal a strong dependence of the torsional response on the rotational phase angle Ψ0 between adjacent nucleosomes. Extreme values of Ψ0 lead to asymmetric, bell-shaped extension-rotation profiles with sharp maxima shifted toward positive or negative rotations, depending on the sign of Ψ0, and to fast, irregular propagation of DNA twist. In contrast, moderate Ψ0 yield more symmetric profiles with broad maxima and slow, uniform propagation of twist. 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. Our results also explain the torsional resilience of chromatin, reconcile differences between experimentally measured extension-rotation profiles, and suggest a role of torsional stresses in regulating chromatin assembly and organization.

Duke Scholars

Author Gaurav Arya Thomas Lord Department of Mechanical Engineering and Materia ...