A Novel Bifunctional Histone Protein in Streptomyces: A Candidate for Structural Coupling Between DNA Conformation and Transcription During Development and Stress?

Nucleic Acids Res. 2013 May;41(9):4813-24. doi: 10.1093/nar/gkt180. Epub 2013 Mar 21.

Abstract

Antibiotic-producing Streptomyces are complex bacteria that remodel global transcription patterns and their nucleoids during development. Here, we describe a novel developmentally regulated nucleoid-associated protein, DdbA, of the genus that consists of an N-terminal DNA-binding histone H1-like domain and a C-terminal DksA-like domain that can potentially modulate RNA polymerase activity in conjunction with ppGpp. Owing to its N-terminal domain, the protein can efficiently bind and condense DNA in vitro. Loss of function of this DNA-binding protein results in changes in both DNA condensation during development and the ability to adjust DNA supercoiling in response to osmotic stress. Initial analysis of the DksA-like activity of DdbA indicates that overexpression of the protein suppresses a conditional deficiency in antibiotic production of relA mutants that are unable to synthesise ppGpp, just as DksA overexpression in Escherichia coli can suppress ppGpp(0) phenotypes. The null mutant is also sensitive to oxidative stress owing to impaired upregulation of transcription of sigR, encoding an alternative sigma factor. Consequently, we propose this bifunctional histone-like protein as a candidate that could structurally couple changes in DNA conformation and transcription during the streptomycete life-cycle and in response to stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA, Fungal / chemistry*
  • DNA-Binding Proteins / metabolism
  • Fungal Proteins / chemistry
  • Fungal Proteins / metabolism*
  • Guanosine Tetraphosphate / biosynthesis
  • Histones / chemistry
  • Histones / metabolism*
  • Ligases / genetics
  • Nucleic Acid Conformation
  • Osmotic Pressure
  • Protein Structure, Tertiary
  • Spores, Fungal / physiology
  • Streptomyces coelicolor / genetics*
  • Streptomyces coelicolor / growth & development
  • Streptomyces coelicolor / physiology
  • Stress, Physiological / genetics
  • Transcription, Genetic

Substances

  • DNA, Fungal
  • DNA-Binding Proteins
  • Fungal Proteins
  • Histones
  • Guanosine Tetraphosphate
  • Ligases
  • guanosine 3',5'-polyphosphate synthetases