Determining transcriptional regulator activities is a major focus of systems biology, providing key insight into regulatory mechanisms and co-regulators. For organisms such as Escherichia coli, transcriptional regulator binding site data can be integrated with expression data to infer transcriptional regulator activities. However, for most organisms there is only sparse data on their transcriptional regulators, while their associated binding motifs are largely unknown. Here, we address the challenge of inferring activities of unknown regulators by generating de novo (binding) motifs and integrating with expression data. We identify a number of key regulators active in the metabolic switch, including PhoP with its associated directed repeat PHO box, candidate motifs for two SARPs, a CRP family regulator, an iron response regulator and that for LexA. Experimental validation for some of our predictions was obtained using gel-shift assays. Our analysis is applicable to any organism for which there is a reasonable amount of complementary expression data and for which motifs (either over represented or evolutionary conserved) can be identified in the genome.
PubMed ID: 22406834
Journal: Nucleic Acids Res
Citation: Nucleic Acids Res. 2012 Jul;40(12):5227-39. doi: 10.1093/nar/gks205. Epub 2012 Mar 9.
Date Published: 13th Mar 2012
Authors: M. Iqbal, Y. Mast, R. Amin, D. A. Hodgson, W. Wohlleben, N. J. Burroughs
Created: 3rd Dec 2016 at 20:38