Computational modeling predicts the structure and dynamics of chromatin fiber

The compact form of the chromatin fiber is a critical regulator of fundamental processes such as transcription and replication. These reactions can occur only when the fiber is unraveled and the DNA strands contained within are exposed to interact with nuclear proteins. While progress on identifying the biochemical mechanisms that control localized folding and hence govern access to genetic information continues, the internal structure of the chromatin fiber, let alone the structural pathways for folding and unfolding, remain unknown.

To offer structural insights into how this nucleoprotein complex might be organized, we present a macroscopic computer model describing the mechanics of the chromatin fiber on the polymer level. We treat the core particles as electrostatically charged disks linked via charged elastic DNA segments and surrounded by a microionic hydrodynamic solution. Each nucleosome unit is represented by several hundred charges optimized so that the effective Debye-Hückel electrostatic field matches the field predicted by the nonlinear Poisson-Boltzmann equation. On the basis of Brownian dynamics simulations, we show that oligonucleosomes condense and unfold in a salt-dependent manner analogous to the chromatin fiber.

Our predicted chromatin model shows good agreement with experimental diffusion coefficients and small-angle X-ray scattering data. A fiber of width 30 nm, organized in a compact helical zigzag pattern with about 4 nucleosomes per 10 nm, naturally emerges from a repeating nucleosome folding motif. This fiber has a cross-sectional radius of gyration of R(c) = 8.66 nm, in close agreement with corresponding values for rat thymus and chicken erythrocyte chromatin (8.82 and 8.5 nm, respectively).