Computational modeling predicts the structure and dynamics of chromatin fiber

Background: The compact form of the chromatin fiber is a critical regulator of fundamental processes such as transcription and replication. These reac tions can occur only when the fiber is unraveled and the DNA strands contai ned 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 structur e of the chromatin fiber, let alone the structural pathways for folding and unfolding, remain unknown. Results: To offer structural insights into how this nucleoprotein complex m ight be organized, we present a macroscopic computer model describing the m echanics of the chromatin fiber on the polymer level. We treat the core par ticles as electrostatically charged disks linked via charged elastic DNA se gments and surrounded by a microionic hydrodynamic solution. Each nucleosom e unit is represented by several hundred charges optimized so that the effe ctive Debye-Huckel electrostatic field matches the field predicted by the n onlinear Poisson-Boltzmann equation. On the basis of Brownian dynamics simu lations, we show that oligonucleosomes condense and unfold in a salt-depend ent manner analogous to the chromatin fiber Conclusions: Our predicted chromatin model shows good agreement with experi mental diffusion coefficients and small-angle X-ray scattering data. A fibe r of width 30 nm, organized in a compact helical zigzag pattern with about 4 nucleosomes per 10 nm, naturally emerges from a repeating nucleosome fold ing motif. This fiber has a cross-sectional radius of gyration of R-c = 8.6 6 nm, in close agreement with corresponding values for rat thymus and chick en erythrocyte chromatin (8.82 and 8.5 nm, respectively).