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 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.
Results: 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.
Conclusions: 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 Rc = 8.66 nm, in close agreement with corresponding
values for rat thymus and chicken erythrocyte chromatin (8.82 and 8.5 nm,
respectively).
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