Dept. Molecular Pharmacology, Stanford University School of Medicine, Stanford, CA 94305-5332
Edited by Sherman M. Weissman, Yale University School of Medicine, New Haven, CT, and approved September 10, 1998 (received for review July 8, 1998).
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.
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