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Nucleosome free regions in yeast promoters result from competitive binding of transcription factors that interact with chromatin modifiers

Ozonov, Evgeniy A. and van Nimwegen, Erik. (2013) Nucleosome free regions in yeast promoters result from competitive binding of transcription factors that interact with chromatin modifiers. PLoS Computational Biology, Vol. 9, H. 8 , e1003181.

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Official URL: http://edoc.unibas.ch/dok/A6194577

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Abstract

Because DNA packaging in nucleosomes modulates its accessibility to transcription factors (TFs), unraveling the causal determinants of nucleosome positioning is of great importance to understanding gene regulation. Although there is evidence that intrinsic sequence specificity contributes to nucleosome positioning, the extent to which other factors contribute to nucleosome positioning is currently highly debated. Here we obtained both in vivo and in vitro reference maps of positions that are either consistently covered or free of nucleosomes across multiple experimental data-sets in Saccharomyces cerevisiae. We then systematically quantified the contribution of TF binding to nucleosome positioning using a rigorous statistical mechanics model in which TFs compete with nucleosomes for binding DNA. Our results reconcile previous seemingly conflicting results on the determinants of nucleosome positioning and provide a quantitative explanation for the difference between in vivo and in vitro positioning. On a genome-wide scale, nucleosome positioning is dominated by the phasing of nucleosome arrays over gene bodies, and their positioning is mainly determined by the intrinsic sequence preferences of nucleosomes. In contrast, larger nucleosome free regions in promoters, which likely have a much more significant impact on gene expression, are determined mainly by TF binding. Interestingly, of the 158 yeast TFs included in our modeling, we find that only 10-20 significantly contribute to inducing nucleosome-free regions, and these TFs are highly enriched for having direct interactions with chromatin remodelers. Together our results imply that nucleosome free regions in yeast promoters results from the binding of a specific class of TFs that recruit chromatin remodelers.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Computational & Systems Biology > Bioinformatics (van Nimwegen)
UniBasel Contributors:van Nimwegen, Erik
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Library of Science
ISSN:1553-734X
e-ISSN:1553-7358
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:12 Oct 2017 10:12
Deposited On:06 Dec 2013 09:35

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