Gene regulation at the single-cell level

Nitzan Rosenfeld, Jonathan W Young, Uri Alon, Peter S Swain, Michael B Elowitz

Research output: Contribution to journalArticlepeer-review

Abstract

The quantitative relation between transcription factor concentrations and the rate of protein production from downstream genes is central to the function of genetic networks. Here we show that this relation, which we call the gene regulation function (GRF), fluctuates dynamically in individual living cells, thereby limiting the accuracy with which transcriptional genetic circuits can transfer signals. Using fluorescent reporter genes and fusion proteins, we characterized the bacteriophage lambda promoter P(R) in Escherichia coli. A novel technique based on binomial errors in protein partitioning enabled calibration of in vivo biochemical parameters in molecular units. We found that protein production rates fluctuate over a time scale of about one cell cycle, while intrinsic noise decays rapidly. Thus, biochemical parameters, noise, and slowly varying cellular states together determine the effective single-cell GRF. These results can form a basis for quantitative modeling of natural gene circuits and for design of synthetic ones.
Original languageEnglish
Pages (from-to)1962-5
Number of pages4
JournalScience
Volume307
Issue number5717
DOIs
Publication statusPublished - 2005

Keywords

  • Bacterial Proteins
  • Bacteriophage lambda
  • Cell Cycle
  • DNA-Binding Proteins
  • Escherichia coli
  • Escherichia coli Proteins
  • Fluorescence
  • Gene Expression Regulation, Bacterial
  • Green Fluorescent Proteins
  • Image Processing, Computer-Assisted
  • Luminescent Proteins
  • Mathematics
  • Microscopy, Fluorescence
  • Models, Genetic
  • Promoter Regions, Genetic
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Signal Transduction
  • Transcription Factors
  • Transcription, Genetic
  • Viral Proteins
  • Viral Regulatory and Accessory Proteins

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