Backup in gene regulatory networks explains differences between binding and knockout results
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 ge...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2009-06-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.1038/msb.2009.33 |
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| _version_ | 1849225767914831872 |
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| author | Anthony Gitter Zehava Siegfried Michael Klutstein Oriol Fornes Baldo Oliva Itamar Simon Ziv Bar‐Joseph |
| author_facet | Anthony Gitter Zehava Siegfried Michael Klutstein Oriol Fornes Baldo Oliva Itamar Simon Ziv Bar‐Joseph |
| author_sort | Anthony Gitter |
| collection | DOAJ |
| 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. |
| format | Article |
| id | doaj-art-63fb08a5ee3c4e54b24c4283483f727e |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2009-06-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-63fb08a5ee3c4e54b24c4283483f727e2025-08-24T11:59:04ZengSpringer NatureMolecular Systems Biology1744-42922009-06-01511710.1038/msb.2009.33Backup in gene regulatory networks explains differences between binding and knockout resultsAnthony Gitter0Zehava Siegfried1Michael Klutstein2Oriol Fornes3Baldo Oliva4Itamar Simon5Ziv Bar‐Joseph6Computer Science Department, School of Computer Science, Carnegie Mellon UniversityDepartment of Molecular Biology, Hebrew University Medical SchoolDepartment of Molecular Biology, Hebrew University Medical SchoolDepartment of Experimental Sciences and Health, Municipal Institute for Medical Research (IMIM‐Hospital del Mar)Department of Experimental Sciences and Health, Pompeu Fabra UniversityDepartment of Molecular Biology, Hebrew University Medical SchoolComputer Science Department, School of Computer Science, Carnegie Mellon UniversityAbstract 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.https://doi.org/10.1038/msb.2009.33backup mechanismsparalogsprotein interactions |
| spellingShingle | Anthony Gitter Zehava Siegfried Michael Klutstein Oriol Fornes Baldo Oliva Itamar Simon Ziv Bar‐Joseph Backup in gene regulatory networks explains differences between binding and knockout results Molecular Systems Biology backup mechanisms paralogs protein interactions |
| title | Backup in gene regulatory networks explains differences between binding and knockout results |
| title_full | Backup in gene regulatory networks explains differences between binding and knockout results |
| title_fullStr | Backup in gene regulatory networks explains differences between binding and knockout results |
| title_full_unstemmed | Backup in gene regulatory networks explains differences between binding and knockout results |
| title_short | Backup in gene regulatory networks explains differences between binding and knockout results |
| title_sort | backup in gene regulatory networks explains differences between binding and knockout results |
| topic | backup mechanisms paralogs protein interactions |
| url | https://doi.org/10.1038/msb.2009.33 |
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