Iqbal, Mudassar, Mast, Yvonne, Amin, Rafat, Hodgson, D. A. (David A.), Wohlleben, W. and Burroughs, Nigel John. (2012) Extracting regulator activity profiles by integration of de novo motifs and expression data : characterizing key regulators of nutrient depletion responses in Streptomyces coelicolor. Nucleic Acids Research, Vol.40 (No.12). pp. 5227-5239. ISSN 0305-1048

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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.

Item Type:	Journal Article
Subjects:	Q Science > QH Natural history > QH426 Genetics
Divisions:	Faculty of Science > Life Sciences (2010- ) Faculty of Science > Centre for Systems Biology
Library of Congress Subject Headings (LCSH):	Genetic transcription -- Regulation, Gene expression, Streptomyces coelicolor -- Genetics
Journal or Publication Title:	Nucleic Acids Research
Publisher:	Oxford University Press
ISSN:	0305-1048
Date:	2012
Volume:	Vol.40
Number:	No.12
Page Range:	pp. 5227-5239
Identification Number:	10.1093/nar/gks205
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access
Funder:	Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), Pakistan. Higher Education Commission, Dow University of Health Sciences, Sixth Framework Programme (European Commission) (FP6)
Grant number:	BB/FF003498/1 (BBSRC), 0315931 (FP6)
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URI:	http://wrap.warwick.ac.uk/id/eprint/48059

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