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Abstract
BackgroundA nucleosome is the fundamental repeating unit of the eukaryotic chromosome. It has been shown that the positioning of a majority of nucleosomes is primarily controlled by factors other than the intrinsic preference of the DNA sequence. One of the key questions in this context is the role, if any, that can be played by the variability of nucleosomal DNA structure.ResultsIn this study, we have addressed this question by analysing the variability at the dinucleotide and trinucleotide as well as longer length scales in a dataset of nucleosome X-ray crystal structures. We observe that the nucleosome structure displays remarkable local level structural versatility within the B-DNA family. The nucleosomal DNA also incorporates a large number of kinks.ConclusionsBased on our results, we propose that the local and global level versatility of B-DNA structure may be a significant factor modulating the formation of nucleosomes in the vicinity of high-plasticity genes, and in varying the probability of binding by regulatory proteins. Hence, these factors should be incorporated in the prediction algorithms and there may not be a unique 'template' for predicting putative nucleosome sequences. In addition, the multimodal distribution of dinucleotide parameters for some steps and the presence of a large number of kinks in the nucleosomal DNA structure indicate that the linear elastic model, used by several algorithms to predict the energetic cost of nucleosome formation, may lead to incorrect results.
Highlights
IntroductionIt has been shown that the positioning of a majority of nucleosomes is primarily controlled by factors other than the intrinsic preference of the DNA sequence
A nucleosome is the fundamental repeating unit of the eukaryotic chromosome
Our analysis shows that even for identical sequences, there is significant local level structural variation and some amount of variation at longer length scales, indicating that there is a thermodynamic ensemble of local level structures that can give rise to the core nucleosome structure
Summary
It has been shown that the positioning of a majority of nucleosomes is primarily controlled by factors other than the intrinsic preference of the DNA sequence. One of the key questions in this context is the role, if any, that can be played by the variability of nucleosomal DNA structure. Formation of a large number of nucleosomes is primarily controlled by factors other than the nucleosome sequence [12,13,14] In this context, one needs to ask what role, if any, is played by the structural variability of nucleosomal DNA in the formation of these nucleosomes. The nucleosome structure at the local level is described in terms of dinucleotide step parameters tilt, roll, twist, shift, slide and rise that quantify the motion between adjacent basepair planes [16]. Analysis of data from nucleosome crystal structures along with that from molecular dynamics simulations of the nucleosome structure have indicated that the distributions of roll, twist and slide are conserved, while tilt, shift and rise are relatively free [19]
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