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PLoS One. 2015 Apr 15;10(4):e0122479. doi: 10.1371/journal.pone.0122479. eCollection 2015.

Genome-wide analysis of in vivo binding of the master regulator DasR in Streptomyces coelicolor identifies novel non-canonical targets.

Author information

1
Molecular Biotechnology, Institute of Biology Leiden, Leiden University, PO Box 9502, 2300 RA Leiden, The Netherlands.
2
Department of Microbial and Cellular Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU2 7XH, United Kingdom.
3
Department of Oecotrophologie, Münster University of Applied Sciences, Corrensstr. 25, 48149 Münster, Germany.
4
Centre for Protein Engineering, Université de Liège, Institut de Chimie B6a, Sart-Tilman, B-4000 Liège, Belgium.

Abstract

Streptomycetes produce a wealth of natural products, including over half of all known antibiotics. It was previously demonstrated that N-acetylglucosamine and secondary metabolism are closely entwined in streptomycetes. Here we show that DNA recognition by the N-acetylglucosamine-responsive regulator DasR is growth-phase dependent, and that DasR can bind to sites in the S. coelicolor genome that have no obvious resemblance to previously identified DasR-responsive elements. Thus, the regulon of DasR extends well beyond what was previously predicted and includes a large number of genes with functions far removed from N-acetylglucosamine metabolism, such as genes for small RNAs and DNA transposases. Conversely, the DasR regulon during vegetative growth largely correlates to the presence of canonical DasR-responsive elements. The changes in DasR binding in vivo following N-acetylglucosamine induction were studied in detail and a possible molecular mechanism by which the influence of DasR is extended is discussed. Discussion of DasR binding was further informed by a parallel transcriptome analysis of the respective cultures. Evidence is provided that DasR binds directly to the promoters of all genes encoding pathway-specific regulators of antibiotic production in S. coelicolor, thereby providing an exquisitely simple link between nutritional control and secondary metabolism.

PMID:
25875084
PMCID:
PMC4398421
DOI:
10.1371/journal.pone.0122479
[Indexed for MEDLINE]
Free PMC Article

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