Abstract
BackgroundNucleosome distribution along chromatin dictates genomic DNA accessibility and thus profoundly influences gene expression. However, the underlying mechanism of nucleosome formation remains elusive. Here, taking a structural perspective, we systematically explored nucleosome formation potential of genomic sequences and the effect on chromatin organization and gene expression in S. cerevisiae.ResultsWe analyzed twelve structural features related to flexibility, curvature and energy of DNA sequences. The results showed that some structural features such as DNA denaturation, DNA-bending stiffness, Stacking energy, Z-DNA, Propeller twist and free energy, were highly correlated with in vitro and in vivo nucleosome occupancy. Specifically, they can be classified into two classes, one positively and the other negatively correlated with nucleosome occupancy. These two kinds of structural features facilitated nucleosome binding in centromere regions and repressed nucleosome formation in the promoter regions of protein-coding genes to mediate transcriptional regulation. Based on these analyses, we integrated all twelve structural features in a model to predict more accurately nucleosome occupancy in vivo than the existing methods that mainly depend on sequence compositional features. Furthermore, we developed a novel approach, named DLaNe, that located nucleosomes by detecting peaks of structural profiles, and built a meta predictor to integrate information from different structural features. As a comparison, we also constructed a hidden Markov model (HMM) to locate nucleosomes based on the profiles of these structural features. The result showed that the meta DLaNe and HMM-based method performed better than the existing methods, demonstrating the power of these structural features in predicting nucleosome positions.ConclusionsOur analysis revealed that DNA structures significantly contribute to nucleosome organization and influence chromatin structure and gene expression regulation. The results indicated that our proposed methods are effective in predicting nucleosome occupancy and positions and that these structural features are highly predictive of nucleosome organization.The implementation of our DLaNe method based on structural features is available online.
Highlights
Nucleosome distribution along chromatin dictates genomic DNA accessibility and profoundly influences gene expression
We systematically investigated twelve structural features related to intrinsic flexibility, curvature and energy of DNA sequence, and analyzed their relation with nucleosome occupancy, chromatin organization and transcriptional regulation across the entire S. cerevisiae genome
As enzyme Dnase I is inclined to bind to the minor groove and to cut DNA that is bent, Dnase I cutting frequencies measure the bendability of DNA sequences [31]
Summary
Nucleosome distribution along chromatin dictates genomic DNA accessibility and profoundly influences gene expression. Taking a structural perspective, we systematically explored nucleosome formation potential of genomic sequences and the effect on chromatin organization and gene expression in S. cerevisiae. In. Besides a multitude of factors, including chromatin remodelers [3,4,5] and specific DNA-binding proteins [6,7], intrinsic DNA sequence preferences have been the focus of recent experimental and bioinformatical studies, which concern how and to what extent sequence features contribute to nucleosome organization [8,9,10,11,12,13,14]. It has been demonstrated that DNA sequence preferences for certain sequence motifs are not the major determinants of nucleosome organization [16,17], which raise a question about the role of the structural variability of DNA sequences in the formation of nucleosomes [10,18,19,20]
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