Influence of nucleosome structure on the three-dimensional folding of idealized minichromosomes

Background: The closed circular, multinucleosome-bound DNA comprising a min ichromosome provides one of the best known examples of chromatin organizati on beyond the wrapping of the double helix around the core of histone prote ins. This higher level of chain folding is governed by the topology of the constituent nucleosomes and the spatial disposition of the intervening prot ein-free DNA linkers. Results: By simplifying the protein-DNA assembly to an alternating sequence of virtual bonds, the organization of a string of nucleosomes on the minic hromosome can be treated by analogy to conventional chemical depictions of macromolecular folding in terms of the bond lengths, valence angles, and to rsions of the chain. If the nucleosomes are evenly spaced and the linkers a re sufficiently short, regular minichromosome structures can be identified from analytical expressions that relate the lengths and angles formed by th e virtual bonds spanning the nucleosome-linker repeating units to the pitch and radius of the organized quaternary structures that they produce. Conclusions: The resulting models with 4-24 bound nucleosomes illustrate ho w a minichromosome can adopt the low-writhe folding motifs deduced from bio chemical studies, and account for published images of the 30 nm chromatin f iber and the simian virus 40 (SV40) nucleohistone core. The marked sensitiv ity of global folding to the degree of protein-DNA interactions and the ass umed nucleosomal shape suggest potential mechanisms for chromosome rearrang ements upon histone modification.