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Topological Polymorphism of the Two-start Chromatin Fiber

Overview
Journal Biophys J
Publisher Cell Press
Specialty Biophysics
Date 2015 May 21
PMID 25992737
Citations 31
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Abstract

Specific details concerning the spatial organization of nucleosomes in 30 nm fibers remain unknown. To investigate this, we analyzed all stereochemically possible configurations of two-start nucleosome fibers with short DNA linkers L = 13-37 bp (nucleosome repeat length (NRL) = 160-184 bp). Four superhelical parameters-inclination of nucleosomes, twist, rise, and diameter-uniquely describe a regular symmetric fiber. The energy of a fiber is defined as the sum of four terms: elastic energy of the linker DNA, steric repulsion, electrostatics, and a phenomenological (H4 tail-acidic patch) interaction between two stacked nucleosomes. By optimizing the fiber energy with respect to the superhelical parameters, we found two types of topological transition in fibers (associated with the change in inclination angle): one caused by an abrupt 360° change in the linker DNA twisting (change in the DNA linking number, ΔLk = 1), and another caused by overcrossing of the linkers (ΔLk = 2). To the best of our knowledge, this topological polymorphism of the two-start fibers was not reported in the computations published earlier. Importantly, the optimal configurations of the fibers with linkers L = 10n and 10n + 5 bp are characterized by different values of the DNA linking number-that is, they are topologically different. Our results are consistent with experimental observations, such as the inclination 60° to 70° (the angle between the nucleosomal disks and the fiber axis), helical rise, diameter, and left-handedness of the fibers. In addition, we make several testable predictions, among them different degrees of DNA supercoiling in fibers with L = 10n and 10n + 5 bp, different flexibility of the two types of fibers, and a correlation between the local NRL and the level of transcription in different parts of the yeast genome.

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