Graded transcriptional response to different concentrations of a single transactivator.
Threshold mechanisms of transcriptional activation are thought to be critical for translating continuous gradients of extracellular signals into discrete all-or-none cellular responses, such as mitogenesis and differentiation. Indeed, unequivocal evidence for a graded transcriptional response in which the concentration of inducer directly correlates with the level of gene expression in individual eukaryotic cells is lacking. By using a novel binary tetracycline regulatable retroviral vector system, we observed a graded rather than a threshold mechanism of transcriptional activation in two different model systems. When polyclonal populations of cells were analyzed at the single cell level, a dose-dependent, stepwise increase in expression of the reporter gene, green fluorescent protein (GFP), was observed by fluorescence-activated cell sorting. These data provide evidence that, in addition to the generally observed all-or-none switch, the basal transcription machinery also can respond proportionally to changes in concentration of extracellular inducers and trancriptional activators.
Kringstein
A M
AM
Department of Molecular Pharmacology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305-5332, USA.
Rossi
F M
FM
Hofmann
A
A
Blau
H M
HM
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D015534:Trans-Activators / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics*
D008164:Luminescent Proteins; D015534:Trans-Activators; D049452:Green Fluorescent Proteins