Topological polymorphism of two-start nucleosome fibers: A stereochemical analysis

Authors

• D Norouzi
• A Katebi
• T Nikitina
• VB Zhurkin

Abstract

Specific details concerning the spatial organization of nucleosomes in 30-nm fibers remain unknown. We analyzed all stereochemically possible configurations of two-start nucleosome fibers with short DNA linkers L = 13-37 bp. In our model, the energy of fiber consists of elastic energy of the linker DNA, steric repulsion, electrostatics, and H4 tail-acidic patch interactions. By optimizing the fiber energy with respect to the superhelical parameters, we found two topological families, or topoisomers of the fibers. The first family is characterized by the linking number per nucleosome value, dLk ~ -1 (T1), and the second family by dLk ~ -2 (T2). Importantly, the optimal conformations with linkers L = 10n and 10n+5 bp belong to different topological families. The topoisomers from family T2 were observed earlier, while family T1 is entirely novel. Our results are consistent with the observed inclination angle 60°-70° (the angle between the nucleosomal disks and the fiber axis), helical rise, diameter and left-handedness of the fibers. The topological and structural aspects of our findings were tested in two ways. First, using topological gel assays, we showed that the fibers with L = 10n and 10n+5 bp have different supercoiling density. Second, we predicted that the novel T1 topoisomers are formed in the actively transcribed parts of genome. Analyzing the local NRL (nucleosome repeat length) in the highly and lowly transcribed yeast genes, we confirmed this prediction. We suggest that the topological polymorphism of chromatin fibers described here may be directly related to transcription regulation in eukaryotes.

Scientific Focus Area: Chromosome Biology

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