Rigid assembly and Monte Carlo models of stable and unstable chromatin structures: the effect of nucleosomal spacing

Coarse-grained models are used to assess the packing of the 30-nm chromatin fiber. First, rigid assembly models for nucleosomal repeats from 155 to 211 bp are built using the crystal structure of the mononucleosome and attached straight stretches of B-DNA. The resulting fiber conformations are analyzed for static clashes and classified into stable and unstable structures. The effect of flexibility and thermal fluctuations is then taken into account by conducting Monte Carlo simulations of chromatin fiber models. Here the DNA is approximated by a flexible polymer chain with Debye–Huckel electrostatics, the geometry of the linker DNA connecting the nucleosomes is based on a two-angle zigzag model, and nucleosomes are represented by flat ellipsoids interacting via an attractive Gay–Berne potential. Unstable fibers occur at a particular repeat length period of 10 bp. Also, the regions of densely compacted fibers repeat at intervals of 10 bp. Besides one- and two-start helical zigzag structures, we show evidence for possible three-start structures, which have not been reported in experiments yet. Finally, we show that a local opening of the linker DNA at the nucleosome core—as probably occurs upon histone acetylation—leads to more open and flexible structures.