Torsional behavior of chromatin is modulated by rotational phasing of nucleosomes.
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.
Affiliation: Department of NanoEngineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0448, USA.Show MeSH
Related in: MedlinePlus
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).
Affiliation: Department of NanoEngineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0448, USA.