Gene

Linguistics

Philosophy

Biology

RNA polymerase II

Transcription (linguistics)

Sigma factor

Promoter

Computational biology

Bacterial transcription

Genetics

Transcription factor

Synthetic biology

RNA polymerase

Gene expression

Nature Communications

Transcription rates are regulated by the interactions between RNA polymerase, sigma factor, and promoter DNA sequences in bacteria. However, it remains unclear how non-canonical sequence motifs collectively control transcription rates. Here, we combine massively parallel assays, biophysics, and machine learning to develop a 346-parameter model that predicts site-specific transcription initiation rates for any σ 70 promoter sequence, validated across 22132 bacterial promoters with diverse sequences. We apply the model to predict genetic context effects, design σ 70 promoters with desired transcription rates, and identify undesired promoters inside engineered genetic systems. The model provides a biophysical basis for understanding gene regulation in natural genetic systems and precise transcriptional control for engineering synthetic genetic systems.

Automated model-predictive design of synthetic promoters to control transcriptional profiles in bacteria