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Significance Cells respond to nutritional challenges by dramatically reprogramming their transcriptomes. In bacteria, transcriptional regulators are often pleiotropic, complicating identification of direct versus indirect effects. Here, we present the genome-wide transcriptional profile resulting from RNA polymerase (RNAP) binding by ppGpp, a transcription regulator found throughout the bacterial domain of life. Most of the more than 750 transcripts identified here were not identified as regulated by ppGpp in previous studies. The excellent correlation between the genes identified as regulated by ppGpp in our RNA-seq analysis and promoters regulated directly by ppGpp in vitro facilitated identification of sequence features distinguishing inhibited, activated, and unregulated promoters from each other, providing tools for future mechanistic studies of ppGpp action.

Genome-wide effects on Escherichia coli transcription from ppGpp binding to its two sites on RNA polymerase