Backup in gene regulatory networks explains differences between binding and knockout results.
Mol Syst Biol
; 5: 276, 2009.
Article
en En
| MEDLINE
| ID: mdl-19536199
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Unión Proteica
/
Genómica
/
Redes Reguladoras de Genes
/
Técnicas de Inactivación de Genes
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Mol Syst Biol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOTECNOLOGIA
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos