Cell fate potentials and switching kinetics uncovered in a classic bistable genetic switch

Nat Commun. 2018 Jul 17;9(1):2787. doi: 10.1038/s41467-018-05071-1.

Abstract

Bistable switches are common gene regulatory motifs directing two mutually exclusive cell fates. Theoretical studies suggest that bistable switches are sufficient to encode more than two cell fates without rewiring the circuitry due to the non-equilibrium, heterogeneous cellular environment. However, such a scenario has not been experimentally observed. Here by developing a new, dual single-molecule gene-expression reporting system, we find that for the two mutually repressing transcription factors CI and Cro in the classic bistable bacteriophage λ switch, there exist two new production states, in which neither CI nor Cro is produced, or both CI and Cro are produced. We construct the corresponding potential landscape and map the transition kinetics among the four production states. These findings uncover cell fate potentials beyond the classical picture of bistable switches, and open a new window to explore the genetic and environmental origins of the cell fate decision-making process in gene regulatory networks.

Publication types

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

MeSH terms

  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Bacteriophage lambda / genetics*
  • Bacteriophage lambda / metabolism
  • Escherichia coli K12 / genetics*
  • Escherichia coli K12 / metabolism
  • Escherichia coli K12 / virology
  • Gene Regulatory Networks*
  • Genes, Reporter
  • Genes, Switch*
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Viral Regulatory and Accessory Proteins / genetics*
  • Viral Regulatory and Accessory Proteins / metabolism

Substances

  • Bacterial Proteins
  • Luminescent Proteins
  • Membrane Proteins
  • Protein Isoforms
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Tsr protein, Bacteria
  • Viral Regulatory and Accessory Proteins
  • phage repressor proteins
  • red fluorescent protein
  • yellow fluorescent protein, Bacteria