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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosamine / metabolism
  • Anti-Bacterial Agents / metabolism
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Bacterial
  • Genome, Bacterial / genetics*
  • Oligonucleotide Array Sequence Analysis
  • Promoter Regions, Genetic / genetics
  • Protein Binding
  • Regulon / genetics
  • Response Elements / genetics*
  • Streptomyces coelicolor / genetics*
  • Streptomyces coelicolor / metabolism
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Transcription Factors
  • Acetylglucosamine