Backup in gene regulatory networks explains differences between binding and/nknockout results
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- dc.contributor.author Gitter, Anthonyca
- dc.contributor.author Siegfried, Zehavaca
- dc.contributor.author Klutstein, Michaelca
- dc.contributor.author Fornés Crespo, Oriol, 1983-ca
- dc.contributor.author Oliva Miguel, Baldomeroca
- dc.contributor.author Simon, Itamarca
- dc.contributor.author Bar-Joseph, Zivca
- dc.date.accessioned 2016-02-16T08:19:31Z
- dc.date.available 2016-02-16T08:19:31Z
- dc.date.issued 2009ca
- dc.description.abstract The complementarity of gene expression and protein-DNA interaction data led to several successful models of biological systems. However, recent studies in multiple species raise doubts about the relationship between these two datasets. These studies show that the overwhelming majority of genes bound by a particular transcription factor (TF) are not affected when that factor is knocked out. Here, we show that this surprising result can be partially explained by considering the broader cellular context in which TFs operate. Factors whose functions are not backed up by redundant paralogs show a fourfold increase in the agreement between their bound targets and the expression levels of those targets. In addition, we show that incorporating protein interaction networks provides physical explanations for knockout effects. New double knockout experiments support our conclusions. Our results highlight the robustness provided by redundant TFs and indicate that in the context of diverse cellular systems, binding is still largely functional.
- dc.description.sponsorship This work was supported in part by NIH grant 1RO1 GM085022 and NSF CAREER award 0448453 to ZBJ. In addition, this material is based on work supported under a National Science Foundation Graduate Research Fellowship to AG
- dc.format.mimetype application/pdfca
- dc.identifier.citation Gitter A, Siegfried Z, Klutstein M, Fornes O, Oliva B, Simon I et al. Backup in gene regulatory networks explains differences between binding and/nknockout results. Mol Syst Biol. 2009;5:276. DOI: 10.1038/msb.2009.33ca
- dc.identifier.doi http://dx.doi.org/10.1038/msb.2009.33
- dc.identifier.issn 1744-4292ca
- dc.identifier.uri http://hdl.handle.net/10230/25829
- dc.language.iso engca
- dc.publisher EMBO Pressca
- dc.relation.ispartof Molecular Systems Biology. 2009;5:276
- dc.rights Copyright © 2009 EMBO and Nature Publishing Group. This is an open‐access article distributed under the terms of the Creative Commons Attribution License, which permits distribution, and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation without specific permissionca
- dc.rights.accessRights info:eu-repo/semantics/openAccessca
- dc.rights.uri http://creativecommons.org/licenses/by-nc-sa/3.0/
- dc.subject.other Genòmica -- Metodologia
- dc.subject.other Proteïnes -- Fixació
- dc.title Backup in gene regulatory networks explains differences between binding and/nknockout resultsca
- dc.type info:eu-repo/semantics/articleca
- dc.type.version info:eu-repo/semantics/publishedVersionca