Biophysical modeling reveals the transcriptional regulatory mechanism of Spo0A, the master regulator in starving <i>Bacillus subtilis</i>

Cell differentiation is often critical for survival. In bacteria, differentiation decisions are controlled by transcriptional master regulators under transcriptional feedback control. Therefore, understanding how master regulators are transcriptionally regulated is required to understand differentiation. However, in many cases, the underlying regulation is complex, with multiple transcription factor binding sites and multiple promoters, making it challenging to dissect the exact mechanisms. Here, we address this problem for the <i>Bacillus subtilis</i> master regulator Spo0A. Using a biophysical model, we quantitatively characterize the effect of individual transcription factor binding sites on each <i>spo0A</i> promoter. Furthermore, the model allows us to identify the specific transcription step that is affected by transcription factor binding. Such a model is promising for the quantitative study of a wide range of master regulators involved in transcriptional feedback.