Nucleic Acids Research Advance Access published online on May 17, 2008
Nucleic Acids Research, doi:10.1093/nar/gkn262
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Genomics |
DNA physical properties determine nucleosome occupancy from yeast to fly
1Laboratoire Statistique et Génome, CNRS/INRA/UEVE, 523 place des Terrasses, 91000 Evry, 2Laboratoire Joliot-Curie and Laboratoire de Physique, ENS-Lyon, 46 allée d'I;talie, 69364 Lyon Cedex 07, 3Centre de Génétique Moléculaire, CNRS, Allée de la Terrasse, 91198 Gif-sur-Yvette and 4Institut Jacques Monod, CNRS, Universités Paris 6-7, 2 Place Jussieu, 75251 Paris Cedex 05, France
*To whom correspondence should be addressed. Tel: +33 144 275707; Fax: +33 144 275716; Email: grange{at}univ-paris-diderot.fr
Received January 7, 2008. Revised April 17, 2008. Accepted April 21, 2008.
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.
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint Authors.
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