Genome-wide distribution of AdpA, a global regulator for secondary metabolism and morphological differentiation in Streptomyces, revealed the extent and complexity of the AdpA regulatory network

DNA Res. 2012 Jun;19(3):259-73. doi: 10.1093/dnares/dss010. Epub 2012 Mar 26.

Abstract

AdpA is a global transcriptional activator triggering morphological differentiation and secondary metabolism in Streptomyces griseus. AdpA influences the expression of >1000 genes; however, the overall picture of the AdpA regulon remains obscure. Here, we took snapshots of the distribution of AdpA across the chromosome in living S. griseus cells using chromatin immunoprecipitation/chromatin affinity precipitation-seq analysis. In both liquid and solid cultures, AdpA bound to >1200 similar sites, which were located on not only in putative regulatory regions (65%), but also in regions (35%) that appeared not to affect transcription. Transcriptome analysis indicated that ~40% of the AdpA-binding sites in putative regulatory regions were involved in gene regulation. AdpA was indicated to act as a transcriptional repressor as well as an activator. Expression profiles of AdpA-target genes were very different between liquid and solid cultures, despite their similar AdpA-binding profiles. We concluded that AdpA directly controls >500 genes in cooperation with other regulatory proteins. A comprehensive competitive gel mobility shift assay of AdpA with 304 selected AdpA-binding sites revealed several unique characteristics of the DNA-binding property of AdpA. This study provides the first experimental insight into the extent of the AdpA regulon, indicating that many genes are under the direct control of AdpA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Chromatin Immunoprecipitation / methods
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation, Bacterial / genetics*
  • Genome, Bacterial / genetics*
  • Regulon / genetics*
  • Sequence Analysis, DNA / methods
  • Streptomyces griseus / genetics*
  • Streptomyces griseus / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcriptome / genetics

Substances

  • AdpA protein, Streptomyces griseus
  • Bacterial Proteins
  • DNA-Binding Proteins
  • Trans-Activators
  • Transcription Factors