Analytical kinetic model of native tandem promoters in E. coli

Closely spaced promoters in tandem formation are abundant in bacteria. We
investigated the evolutionary conservation, biological functions, and the
RNA and single-cell protein expression of genes regulated by tandem
promoters in E. coli. We also studied the sequence (distance between
transcription start sites ‘dTSS’, pause sequences, and distances from
oriC) and potential influence of the input transcription factors of these
promoters. From this, we propose an analytical model of gene expression
based on measured expression dynamics, where RNAP-promoter occupancy times
and dTSS are the key regulators of transcription interference due to TSS
occlusion by RNAP at one of the promoters (when dTSS ≤ 35 bp) and RNAP
occupancy of the downstream promoter (when dTSS > 35 bp). Occlusion
and downstream promoter occupancy are modeled as linear functions of
occupancy time, while the influence of dTSS is implemented by a continuous
step function, fit to in vivo data on mean single-cell protein numbers of
30 natural genes controlled by tandem promoters. The best-fitting step is
at 35 bp, matching the length of DNA occupied by RNAP in the open complex
formation. This model accurately predicts the squared coefficient of
variation and skewness of the natural single-cell protein numbers as a
function of dTSS. Additional predictions suggest that promoters in tandem
formation can cover a wide range of transcription dynamics within
realistic intervals of parameter values. By accurately capturing the
dynamics of these promoters, this model can be helpful to predict the
dynamics of new promoters and contribute to the expansion of the
repertoire of expression dynamics available to synthetic genetic
constructs.