Albany 2015:Book of Abstracts
June 9-13 2015
©Adenine Press (2012)
Topological Polymorphism of Two-start Nucleosome Fibers
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. Four superhelical parameters - inclination of nucleosomes, twist, rise and diameter - uniquely describe a uniform symmetric fiber. In our model, the energy of fiber consists of elastic energy of the linker DNA, steric repulsion, electrostatics, and (H4 tail - acidic patch) interaction between two stacked nucleosomes. By optimizing the fiber energy with respect to the superhelical parameters, we found two topological families of the stereochemically feasible fiber configurations, similar to those predicted by Williams et al. (1986) who used space filling models. The first family is characterized by the linking number per nucleosome, ΔLk ≈ -1, and the second one by ΔLk ≈ -2. This topological polymorphism of the nucleosome fibers was not reported in the computations published earlier. More importantly, we found that the optimal conformations with linkers L = 10n and 10n +5 bp belong to different families (with ΔLk ≈ - 2 and - 1, respectively). The optimal topoisomers for L = 20 and 25 bp are shown below; the extended conformers emphasize the difference between the two families. The topoisomer with ΔLk ≈ -2 and L = 20 bp has been proposed earlier based on the tetra-nucleosome crystal structure (Schalch et al., 2005), whereas the topoisomers with ΔLk ≈ -1 were not observed directly. Note, however, that the classical measurements of the DNA linking number in SV40 minichromosome (Keller et al., 1975) indicate that this topoisomer may be dominant in vivo. Finally, we make several testable predictions: the existence of 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 inter-nucleosome spacing and the level of transcription in different parts of the yeast genome.
T. Schalch, S. Duda, D.F. Sargent, & Timothy J.R. (2005). X-ray structure of a tetranucleosome and its implications for the chromatin fibre. Nature. 436, 138-141.
S.P. Williams, B.D. Athey, L.J. Muglia, R.S. Schappe, A.H. Gough, & Langmore J.P. (1986). Chromatin fibers are left-handed double helices with diameter and mass per unit length that depend on linker length. Biophys J. 49, 233-248.
Laboratory of Cell Biology