Article

DNA physical properties determine nucleosome occupancy from yeast to fly

Laboratoire Statistique et Génome, CNRS/INRA/UEVE, 523 place des Terrasses, 91000 Evry, France.
Nucleic Acids Research (Impact Factor: 9.11). 06/2008; 36(11):3746-56. DOI: 10.1093/nar/gkn262
Source: PubMed

ABSTRACT Nucleosome positioning plays an essential role in cellular processes by modulating accessibility of DNA to proteins. Here, using only sequence-dependent DNA flexibility and intrinsic curvature, we predict the nucleosome occupancy along the genomes of Saccharomyces cerevisiae and Drosophila melanogaster and demonstrate the predictive power and universality of our model through its correlation with experimentally determined nucleosome occupancy data. In yeast promoter regions, the computed average nucleosome occupancy closely superimposes with experimental data, exhibiting a <200 bp region unfavourable for nucleosome formation bordered by regions that facilitate nucleosome formation. In the fly, our model faithfully predicts promoter strength as encoded in distinct chromatin architectures characteristic of strongly and weakly expressed genes. We also predict that nucleosomes are repositioned by active mechanisms at the majority of fly promoters. Our model uses only basic physical properties to describe the wrapping of DNA around the histone core, yet it captures a substantial part of chromatin's structural complexity, thus leading to a much better prediction of nucleosome occupancy than methods based merely on periodic curved DNA motifs. Our results indicate that the physical properties of the DNA chain, and not just the regulatory factors and chromatin-modifying enzymes, play key roles in eukaryotic transcription.

Download full-text

Full-text

Available from: Thierry Grange, Jun 28, 2015
0 Followers
 · 
113 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Nucleosome positioning participates in many cellular activities and plays significant roles in regulating cellular processes. With the avalanche of genome sequences generated in the postgenomic age, it is highly desired to develop automated methods for rapidly and effectively identifying nucleosome positioning. Although some computational methods were proposed, most of them were species specific and neglected the intrinsic local structural properties that might play important roles in determining the nucleosome positioning on a DNA sequence. Here a predictor called " INUC-PSEKNC " was developed for predicting nucleosome positioning in Homo sapiens, Caenorhabditis elegans, and Drosophila melanogaster genomes, respectively. In the new predictor, the samples of DNA sequences were formulated by a novel feature-vector called "pseudo k-tuple nucleotide composition", into which six DNA local structural properties were incorporated. It was observed by the rigorous cross-validation tests on the three stringent benchmark datasets that the overall success rates achieved by INUC-PSEKNC in predicting the nucleosome positioning of the aforementioned three genomes were 86.27%, 86.90% and 79.97%, respectively. Meanwhile, the results obtained by INUC-PSEKNC on various benchmark datasets used by the previous investigators for different genomes also indicated that the current predictor remarkably outperformed its counterparts. A user-friendly web-server, INUC-PSEKNC is freely accessible at http://lin.uestc.edu.cn/server/iNuc-PseKNC. hlin@gordonlifescience.org, hlin@uestc.edu.cn (H.L.); greatchen@heuu.edu.cn, wchen@gordonlifescience.org (W.C.); kcchou@gordonlifescience.org (KCC).
    Bioinformatics 02/2014; 30(11). DOI:10.1093/bioinformatics/btu083 · 4.62 Impact Factor
  • Source
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: 10-11bp repeating patterns of the particular dinucleotides were suggested in positioning nucleosomes in eukaryotes. In order to assess the role, the 10-11bp periodicities of the dinucleotides were examined both in human well-positioned nucleosome DNA sequences and in promoter DNA sequences of eight species. Our results indicated that the periodical occurrence of the particular dinucleotides correlates to positioning nucleosome. The signals of 10-11bp periodicities are more pronounced in the nucleosome DNA sequences than in the linker DNA sequences. Near the transcription start site, the signals reveal a similar feature that the nucleosome organization exhibits. But, it seems that the species do not share the same dinucleotides patterns. Furthermore, the dinucleotides patterns are dominant at the specific region of genome, indicating their diverse roles in forming and organizing nucleosomes. Moreover, the 10-11bp periodicities signals near the translation start negatively correlate with gene expression, demonstrating a vital role in transcription regulation. Our study reveals some details about the roles of DNA sequence in positioning nucleosomes.
    Bio Systems 06/2011; 105(3):295-9. DOI:10.1016/j.biosystems.2011.05.016 · 1.47 Impact Factor