Reviewer #1 (Public review): Nonlinear transcriptional responses to gradual modulation of transcription factor dosage

This important work develops a new protocol to experimentally perturb target genes across a quantitative range of expression levels in cell lines.The evidence supporting their new perturbation approach is convincing, and we propose that focusing on single modality (activation or inhibition) would be sufficient to draw their conclusions.The study will be of broad interest to scientists in the fields of functional genomics and biotechnology.