Extracting regulator activity profiles by integration of de novo motifs and expression data: characterizing key regulators of nutrient depletion responses in Streptomyces coelicolor
dc.contributor.author | Iqbal, M | |
dc.contributor.author | Mast, Y | |
dc.contributor.author | Amin, R | |
dc.contributor.author | Hodgson, DA | |
dc.contributor.author | STREAM Consortium | |
dc.contributor.author | Wohlleben, W | |
dc.contributor.author | Burroughs, NJ | |
dc.date.accessioned | 2017-09-26T10:41:51Z | |
dc.date.issued | 2012-02-09 | |
dc.description.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. | en_GB |
dc.description.sponsorship | Biotechnology and Biological Sciences Research Council (BBSRC), UK, grant number BB/FF003498/1, awarded through the ERA-NET SysMO initiative. (to M.I.); Higher Education Commission of Pakistan in collaboration with Dow University of Health Sciences, Karachi, Pakistan, and the ERA-IB Immunotech project (0315931) to R.A. Experimental data was generated under STREAM, an international consortium funded under the ERA-NET SysMO initiative (Systems Biology of Microorganisms) http://www.sysmo.net . Funding for open access charge: Biotechnology and Biological Sciences Research Council (BBSRC). | en_GB |
dc.identifier.citation | Vol. 40 (12), pp. 5227 - 5239 | en_GB |
dc.identifier.doi | 10.1093/nar/gks205 | |
dc.identifier.other | gks205 | |
dc.identifier.uri | http://hdl.handle.net/10871/29536 | |
dc.language.iso | en | en_GB |
dc.publisher | Oxford University Press (OUP) | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/22406834 | en_GB |
dc.rights | © The Author(s) 2012. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. | en_GB |
dc.subject | Bacterial Proteins | en_GB |
dc.subject | Binding Sites | en_GB |
dc.subject | Gene Expression Profiling | en_GB |
dc.subject | Gene Regulatory Networks | en_GB |
dc.subject | Genomics | en_GB |
dc.subject | Glutamic Acid | en_GB |
dc.subject | Nucleotide Motifs | en_GB |
dc.subject | Phosphates | en_GB |
dc.subject | Streptomyces coelicolor | en_GB |
dc.subject | Transcription Factors | en_GB |
dc.subject | Transcriptome | en_GB |
dc.title | Extracting regulator activity profiles by integration of de novo motifs and expression data: characterizing key regulators of nutrient depletion responses in Streptomyces coelicolor | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2017-09-26T10:41:51Z | |
exeter.place-of-publication | England | en_GB |
dc.description | This is the final version of the article. Available from OUP via the DOI in this record. | en_GB |
dc.identifier.journal | Nucleic Acids Research | en_GB |
dc.rights.uri | http://creativecommons.org/licenses/by-nc/3.0 |
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Except where otherwise noted, this item's licence is described as © The Author(s) 2012. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.