Graded transcriptional response to different concentrations of a single transactivator

作者：Andrew M. Kringstein, Fabio M V Rossi, Andreas Hofmann, Helen M. Blau · 发表于：Proceedings of the National Academy of Sciences · 年份：1998 · DOI：10.1073/pnas.95.23.13670 · 被引用次数：97 · 研究领域：Virus-based gene therapy research、Viral Infectious Diseases and Gene Expression in Insects、CRISPR and Genetic Engineering

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.