title: Extracting regulator activity profiles by integration of de novo motifs and expression data: characterizing key regulators of nutrient depletion responses in Streptomyces coelicolor.
abstract: 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.
authors.affiliation: Multidisciplinary Centre for Integrative Biology (MyCIB), School of Biosciences, University of Nottingham, Nottingham, UK. mudassar.iqbal@nottingham.ac.uk
authors.forename: Mudassar
authors.initials: M
authors.lastname: Iqbal
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Mast
authors.forename: Rafat
authors.initials: R
authors.lastname: Amin
authors.forename: David A
authors.initials: DA
authors.lastname: Hodgson
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wohlleben
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Burroughs
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism; D001665:Binding Sites; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D023281:Genomics / Q000379:methods; D018698:Glutamic Acid / Q000378:metabolism; D059372:Nucleotide Motifs; D010710:Phosphates / Q000378:metabolism; D048372:Streptomyces coelicolor / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D001426:Bacterial Proteins; D010710:Phosphates; D014157:Transcription Factors; C061064:PhoP protein, Bacteria; D018698:Glutamic Acid