Using chromosomal lacIQ1 to control expression of genes on high-copy-number plasmids in Escherichia coli

Gene. 1998 Nov 26;223(1-2):221-31. doi: 10.1016/s0378-1119(98)00240-6.

Abstract

Transcription of the lac and the hybrid tac promoters is repressed by the lac repressor and induced by the non-metabolizable substrate IPTG. The degree of repression depends upon the ratio of LacI molecules in a cell to the DNA operator sites. In the absence of an inducer, repression of Ptac on a high-copy-number (hcn) plasmid was equivalent in strains containing lacIQ1 on the chromosome, or lacI+ on the plasmid, but not from strains with lacI+ or lacIQ only on the chromosome. Induction of Ptac on hcn plasmids in strains in which expression was controlled by lacIQ1 occurred at very low inducer concentrations (3-10microM IPTG) and reached levels significantly higher than in strains with lacI+ on the plasmid. Greater than 300-fold induction of a beta-LacZ fusion was observed, and >600-fold induction was estimated from recombinant hemoglobin synthesis. Transcription from PlacIQ1 initiated in the same point as PlacI+, but was 170-fold stronger, consistent with the lac repressor levels required to control LacI-regulated genes on hcn plasmids. The DNA sequence upstream of lacI was used to develop a simple PCR test to identify lacIQ1 by a characteristic 15-bp deletion. This deletion created a consensus -35 hexamer, responsible for the increased lacI transcription, and was easily detectable in a variety of strains. Using lacIQ1 hosts eliminates the requirement to maintain lacI on the plasmid to regulate gene expression on hcn expression plasmids.

MeSH terms

  • Bacterial Proteins / analysis
  • Bacterial Proteins / genetics*
  • Base Sequence
  • Chromosomes, Bacterial
  • Escherichia coli / genetics*
  • Escherichia coli Proteins*
  • Gene Dosage
  • Gene Expression Regulation, Bacterial
  • Isopropyl Thiogalactoside / metabolism
  • Isopropyl Thiogalactoside / pharmacology
  • Lac Repressors
  • Molecular Sequence Data
  • Plasmids / genetics*
  • Repressor Proteins / analysis
  • Repressor Proteins / genetics*
  • Transcription, Genetic

Substances

  • Bacterial Proteins
  • Escherichia coli Proteins
  • Lac Repressors
  • LacI protein, E coli
  • Repressor Proteins
  • Isopropyl Thiogalactoside