Chromatin Structure and Dynamics in Response to External Forces and Torques

Abstract

Chromatin is subjected to myriad forces and torques during DNA repair, transcription, recombination, and replication. Despite the growing realization that such forces and torques play important roles in chromatin function, our understanding of how these perturbations affect chromatin structure and dynamics remains poor. I will describe recent efforts from our group in modeling chromatin structure and dynamics subjected to external torques and forces.First, I will describe Monte Carlo simulations of a mesoscale model of chromatin to study the propagation of DNA twist across nucleosomes [1,2]. The magnitude and sign of the imposed and induced twist on contiguous linker DNAs is found to depend strongly on their relative orientation. Interestingly, the relative sign of the induced and applied twist becomes inverted for a subset of linker orientations. We have characterized twist inversion as a function of linker orientation in a phase diagram and explained its key features using a geometrical model. We also reveal rapid flipping of nucleosomes in response to applied twist, which allows for rapid changes in the overall twist and writhe of nucleosome arrays. Second, I will describe Brownian dynamics simulations of a mesoscale model of the nucleosome to elucidate the dynamics of force-induced unwrapping of DNA from histone octamers [3]. We demonstrate why the first turn of DNA unwraps reversibly from the octamers and the second turn wraps irreversibly, as observed in single-molecule experiments. We also reveal the complex flipping and rocking motions of the octamer accompanying nucleosome unraveling and the role of the strong histone/DNA interactions at the dyad and ∼35 bp from the entry/exit site.1. Grigoryev et al., PNAS 106, 13317 (2009)2. Dobrovolskaia et al., Biophys. J. 99, 3355 (2010)3. Dobrovolskaia & Arya, to be submitted