Nucleosome-induced homology recognition in chromatin

Abstract

One of the least understood properties of chromatin is the ability of its similar regions to recognize each other through weak interactions. Theories based on electrostatic interactions between helical macromolecules suggest that the ability to recognize sequence homology is an innate property of the non-ideal helical structure of DNA. However, this theory does not account for the nucleosomal packing of DNA. Can homologous DNA sequences recognize each other while wrapped up in the nucleosomes? Can structural homology arise at the level of nucleosome arrays? Here, we present a theoretical model for the recognition potential well between chromatin fibres sliding against each other. This well is different from the one predicted for bare DNA; the minima in energy do not correspond to literal juxtaposition, but are shifted by approximately half the nucleosome repeat length. The presence of this potential well suggests that nucleosome positioning may induce mutual sequence recognition between chromatin fibres and facilitate the formation of chromatin nanodomains. This has implications for nucleosome arrays enclosed between CTCF–cohesin boundaries, which may form stiffer stem-like structures instead of flexible entropically favourable loops. We also consider switches between chromatin states, e.g. through acetylation/deacetylation of histones, and discuss nucleosome-induced recognition as a precursory stage of genetic recombination.

Heterochromatin Networks: Topology, Dynamics, and Function (a Working Hypothesis)

“…This drying acts like mild osmotic stress and is reversible by wetting the cells [ 53 ]. In line with these observations, the biophysical study by [ 90 ] suggests that the increased recognition energy of ordered heterochromatic nucleosome arrays more densely packed near CTCF binding sites may favor the tendency to form stem structures (the sites of crystallization?). They are facilitated by the general osmotic stress and confinement pressure in the cell nucleus as well as by the additional pressure of DNA supercoiling acting near CTCF sites due to cohesion molecular motors, which actively form chromatin loops at these sites [ 91 ].…”

“…Elasticity and stiffness are the main biomechanical properties of the cytoskeleton network [ 112 ]. Additionally, flexible-bending rigidity and stickiness are the features of heterochromatin [ 23 , 90 , 113 ]. This would be a prerequisite for the cooperation of the two networks in the regulation of transcriptional pulsing, which is likely started from the nucleolus.…”