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However, even minimal synthetic systems often exhibit unexplained behaviors. In a widely used inducible mammalian expression system, we show that transcriptional responses appear graded and sigmoidal at the population level but are largely all-or-none at the single-cell level. By combining single-cell sorting and single-molecule footprinting with mathematical modeling of transcriptional regulation, we found that this behavior is not caused by bursty transcription or bistability, but by long-lived, chromatin-encoded variability in TF occupancy and activation strength. This variability produced a range of activation thresholds in switch-like single-cell responses that were stable over time, resulting in bimodal gene expression across the population. 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