Lysogen stability is determined by the frequency of activity bursts from the fate-determining gene

Mol Syst Biol. 2010 Nov 30;6:440. doi: 10.1038/msb.2010.96.

Abstract

The ability of living cells to maintain an inheritable memory of their gene-expression state is key to cellular differentiation. Bacterial lysogeny serves as a simple paradigm for long-term cellular memory. In this study, we address the following question: in the absence of external perturbation, how long will a cell stay in the lysogenic state before spontaneously switching away from that state? We show by direct measurement that lysogen stability exhibits a simple exponential dependence on the frequency of activity bursts from the fate-determining gene, cI. We quantify these gene-activity bursts using single-molecule-resolution mRNA measurements in individual cells, analyzed using a stochastic mathematical model of the gene-network kinetics. The quantitative relation between stability and gene activity is independent of the fine details of gene regulation, suggesting that a quantitative prediction of cell-state stability may also be possible in more complex systems.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bacteriophage lambda / genetics
  • Bacteriophage lambda / physiology
  • Escherichia coli / genetics
  • Escherichia coli / physiology
  • Gene Expression Regulation, Bacterial / genetics
  • Gene Expression Regulation, Bacterial / physiology*
  • Genes, Viral / physiology
  • Genome, Bacterial / physiology
  • Genomic Instability / genetics*
  • Lysogeny / genetics*
  • Models, Biological
  • Organisms, Genetically Modified
  • Repressor Proteins / genetics
  • Repressor Proteins / physiology*
  • Viral Regulatory and Accessory Proteins / genetics
  • Viral Regulatory and Accessory Proteins / physiology*

Substances

  • Repressor Proteins
  • Viral Regulatory and Accessory Proteins
  • phage repressor proteins