A deformation energy-based model for predicting nucleosome dyads and occupancy

Abstract

Nucleosome plays an essential role in various cellular processes, such as DNA replication, recombination, and transcription. Hence, it is important to decode the mechanism of nucleosome positioning and identify nucleosome positions in the genome. In this paper, we present a model for predicting nucleosome positioning based on DNA deformation, in which both bending and shearing of the nucleosomal DNA are considered. The model successfully predicted the dyad positions of nucleosomes assembled in vitro and the in vitro map of nucleosomes in Saccharomyces cerevisiae. Applying the model to Caenorhabditis elegans and Drosophila melanogaster, we achieved satisfactory results. Our data also show that shearing energy of nucleosomal DNA outperforms bending energy in nucleosome occupancy prediction and the ability to predict nucleosome dyad positions is attributed to bending energy that is associated with rotational positioning of nucleosomes.

The implication of DNA bending energy for nucleosome positioning and sliding

“…Particularly, bending energy performed very well in the dyad position prediction 46 . Although a number of energetics models were proposed to predict nucleosome-forming ability of DNA sequences 32 – 46 , to our best knowledge, none of them attempted to discuss the link between DNA deformation energy profile and chromatin remodeling. In this study, we characterized distinctly-organized chromatin structure in terms of DNA bending energy, and explored bending energy-related properties in nucleosome sliding.…”

“…A nucleosome consists of a histone octamer and a DNA segment of 147 bp that is sharply bent and tightly wrapped ~1.7 times around the histone octamer in a left-handed superhelix. Two 9-bp ends of nucleosomal DNA have little contribution to its curvature 24 , 46 and hence a 129-bp window is used in bending energy calculation. The bending energy is formulated as where ρ ( i ) and τ ( i ) are, respectively, the predicted roll and tilt angles at dinucleotide step i in a 129-bp DNA segment assumed to be subject to a constraint of curvature of 579°, which is the same as that for the central 129-bp part of the ideal superhelix that best fits the core DNA in the nucleosome core particle 24 ; ρ 0 ( i ) and τ 0 ( i ) are equilibrium values of roll and tilt respectively for the dinucleotide at step i ; k ρ ( i ) and k τ ( i ) are the dinucleotide-dependent force constants.…”

“…For example, the 10-bp periodicity and positioning motifs in nucleosomal DNA facilitate the wrapping of the sequence around a histone octamer by increasing sequence curvature 5 , 24 . Among the existing models 25 – 46 designed to predict nucleosome positions, physical models 32 – 46 are preferable in terms of providing a much deeper and intuitive insight into the nucleosome positioning mechanism. For example, a physical model in which both DNA elastic energy and histone-DNA interaction term used to penalize the deviation of nucleosomal DNA from ideal superhelix were considered successfully predicted in vitro nucleosome positions and free energies 40 .…”

“…Using the model, the authors predicted positions of several nucleosomes with a high accuracy and investigated the nucleosome sliding supposed to take place through twist defect diffusion. In our previous study, we presented a deformation energy model and successfully applied it to the prediction of nucleosome dyad positions and occupancy 46 . Particularly, bending energy performed very well in the dyad position prediction 46 .…”

“…In our previous study, we presented a deformation energy model and successfully applied it to the prediction of nucleosome dyad positions and occupancy 46 . Particularly, bending energy performed very well in the dyad position prediction 46 . Although a number of energetics models were proposed to predict nucleosome-forming ability of DNA sequences 32 – 46 , to our best knowledge, none of them attempted to discuss the link between DNA deformation energy profile and chromatin remodeling.…”