Choreography for nucleosomes: the conformational freedom of the nucleosomal filament and its limitations

Abstract

Eukaryotic DNA is organized into nucleosomes by coiling around core particles of histones, forming a nucleosomal filament. The significance for the conformation of the filament of the DNA entry/exit angle (α) at the nucleosome, the angle of rotation (β) of nucleosomes around their interconnecting DNA (linker DNA) and the length of the linker DNA, has been studied by means of wire models with straight linkers. It is shown that variations in α and β endow the filament with an outstanding conformational freedom when α is increased beyond 60–90°, owing to the ability of the filament to change between forward right-handed and backward left-handed coiling. A wealth of different helical and looped conformations are formed in response to repeated β sequences, and helical conformations are shown to be able to contract to a high density and to associate pairwise into different types of double fibers. Filaments with random β sequences are characterized by relatively stable loop clusters connected by segments of higher flexibility. Displacement of core particles along the DNA in such fibers, combined with limited twisting of the linkers, can generate the β sequence necessary for compaction into a regular helix, thus providing a model for heterochromatinization.

Author response: A simple biophysical model emulates budding yeast chromosome condensation

“…where c 4 is the magnitude of the force, proportional to the distance between beads i, i + 2 and between beads i, i − 2, respectively.û i,i + 2 andû i,i − 2 are dimensionless unit vectors determining the direction of the force (from bead i to i + 2 and from bead i to i − 2, respectively). The force fine-tunes the distribution of the α angle between three consecutive beads and does not serve as a driving factor for any pre-defined local structures: the α angle distribution for our simulated chromosomes has a bell shape curve, which peaks at around 70˚(benchmarked with experimental measurements of the α angle of 75˚, based on the nucleosome crystal structure [Luger et al, 1997]) and tails off at around 20å nd 180˚, consistent with the relative flexibility that is thought to characterize the α angle (Figure 1-figure supplement 2) (Bednar et al, 1998;Engelhardt, 2007). This means that the model does not exclude the possibility of forming small fragments of locally compact structures that resemble the 20-30 nm fibers widely speculated in other models (the α angle of a 30 nm fiber is centered at 36˚or 108˚).…”

“…Nucleosomes exclude each other in space though, during our simulations, the linker DNA can cross itself with a small probability, which, under in vivo conditions would be achieved by the enzyme topoisomerase II. A weak force corrects the angle at which DNA emerges from the nucleosome surface (Luger et al, 1997;Bednar et al, 1998;Engelhardt, 2007) (see 'Materials and methods' for details of the model).…”

Influence of Benzoate on Substituent Benzoic Acids with Implications on Spectroscopic Studies through Inter Molecular Hydrogen Bonding

“…With increase in chain length the influence of benzoate on the core molecule enabled greater degree of conformational freedom [31,32]. These parameters articulate that the benzoate group has successfully disturbed the oriented texture of its molecules to layered texture.…”

Transcription and the aspect ratio of DNA

“…Recently, the energetics of transitions in the supercoiling state have been studied in careful details [36], and the dynamics of supercoils have been observed directly in single-molecule studies [37]. The unfolding of the chromatin fiber remains an interesting subject where there currently is significant progress [38][39][40]. This field remains under ongoing debate [41][42][43].…”