Torsional Behavior of Nucleosome Arrays

Abstract

Genomic DNA is subjected to strong torsional stresses during processes like transcription and replication. Emerging evidence suggests that such torsional stresses might serve critical functions in the cell nucleus. Most experimental and theoretical work so far has focused on understanding the supercoiling of the naked DNA, but little is known about how torsional stresses are stored, propagated, and relieved within the chromatin fiber. Here we investigate the torsional behavior of nucleosome arrays by using Brownian dynamics simulations of a coarse-grained model of chromatin fiber. By rotating one end of the array in a step-wise manner while keeping the other end fixed, we measure the equilibrium extension of the array as a function of the applied twist. The measured twist-extension profiles display an asymmetry shape with a shifted maximal extension. The magnitude and sign of the observed shift depends strongly on the internucleosomal “phase” angle resulting from the helical twist of the linker DNA. Moreover, moderate values of the phase angle lead to broad plateau at the maxima in the twist-extension plots while extreme values of the angle lead to sharper maxima. By tracing different nucleosome states in the rotations, we show that the plateau results from a conformational transition between open and negatively crossed states of individual nucleosomes with a minimal twisting energy cost, explaining high torsional resilience of the array. Indeed, the torsional rigidity of the array extracted from twisting energies is significantly smaller than that of naked DNA. Finally, we construct the kymograph of rotational autocorrelation function for each segment of the array, which clearly visualizes the effect of phase angle on the propagation of twist. This work provides one of the first detailed pictures of supercoiled chromatin and how eukaryotic DNA might relieve its torsional stresses through conformational transitions in the nucleosome.