title: Genome-wide analysis of in vivo binding of the master regulator DasR in Streptomyces coelicolor identifies novel non-canonical targets.
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.
authors: Molecular Biotechnology, Institute of Biology Leiden, Leiden University, PO Box 9502, 2300 RA Leiden, The Netherlands.
authors: Magdalena A
authors: MA
authors: Świątek-Połatyńska
authors: Department of Microbial and Cellular Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU2 7XH, United Kingdom.
authors: Giselda
authors: G
authors: Bucca
authors: Department of Microbial and Cellular Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU2 7XH, United Kingdom.
authors: Emma
authors: E
authors: Laing
authors: Molecular Biotechnology, Institute of Biology Leiden, Leiden University, PO Box 9502, 2300 RA Leiden, The Netherlands.
authors: Jacob
authors: J
authors: Gubbens
authors: Department of Oecotrophologie, Münster University of Applied Sciences, Corrensstr. 25, 48149 Münster, Germany.
authors: Fritz
authors: F
authors: Titgemeyer
authors: Department of Microbial and Cellular Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU2 7XH, United Kingdom.
authors: Colin P
authors: CP
authors: Smith
authors: Centre for Protein Engineering, Université de Liège, Institut de Chimie B6a, Sart-Tilman, B-4000 Liège, Belgium.
authors: Sébastien
authors: S
authors: Rigali
authors: Molecular Biotechnology, Institute of Biology Leiden, Leiden University, PO Box 9502, 2300 RA Leiden, The Netherlands.
authors: Gilles P
authors: GP
authors: van Wezel
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D016680:Genome, Bacterial / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D018085:Regulon / Q000235:genetics; D020218:Response Elements / Q000235:genetics*; D048372:Streptomyces coelicolor / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D014157:Transcription Factors; D000117:Acetylglucosamine