The transcription factor network of E. coli steers global responses to shifts in RNAP concentration

The robustness and sensitivity of gene networks to environmental changes
is critical for cell survival. How gene networks produce specific,
chronologically ordered responses to genome-wide perturbations, while
robustly maintaining homeostasis, remains an open question. We analysed if
short- and mid-term genome-wide responses to shifts in RNA polymerase
(RNAP) concentration are influenced by the known topology and logic of the
transcription factor network (TFN) of Escherichia coli. We found that, at
the gene cohort level, the magnitude of the single-gene, mid-term
transcriptional responses to changes in RNAP concentration can be
explained by the absolute difference between the gene’s numbers of
activating and repressing input transcription factors (TFs).
Interestingly, this difference is strongly positively correlated with the
number of input TFs of the gene. Meanwhile, short-term responses showed
only weak influence from the TFN. Our results suggest that the global
topological traits of the TFN of E. coli shape which gene cohorts respond
to genome-wide stresses.