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

Abstract

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.

A library of reporters of the global regulators of gene expression ofEscherichia coli

“…To further test the efficiency of the GR reporters, we used RNA-seq data from (Almeida et al , 2022) for the GRs genes at two time moments during exponential growth (Methods section “RNA-seq”). Then we performed corresponding GRs’ GFP measurements by spectrophotometry in the same growth conditions and time moments.…”

“…The TFN of E. coli has evolved an out-degree distribution that follows a power law (Almeida et al , 2022), due to which a small fraction of the genes expressing TFs (22 of 216) directly regulate many genes (∼31% of all ∼4747 genes in the genome (RegulonDB 11.1) (Tierrafría et al , 2022). Following the RNA and/or protein levels of each of these GRs is, thus, a key step for dissecting the transcriptional programs of stress response.…”

“…Finally, we also diluted overnight culture cells into fresh LB media to monitor the growth as well as to measure their GFP levels after 60 and 120 minutes. The latter was compared to the RNA-seq data from (Almeida et al , 2022).…”

“…The RNA-seq data used was first published in (Almeida et al , 2022). Briefly, overnight cultured cells were diluted into fresh LB media.…”

Global control of cellular physiology by biomolecular condensates through modulation of electrochemical equilibria

“…Of these, we assessed the expression profiles of genes that can be regulated by the changes of cellular chemical environment, including pathways regulated by ion-dependent transcription factors, osmotic stress and pH. Compared with cells without condensates, cells with condensates upregulated the expression of all genes in Mg ++ transporter pathways (mgt, mgr, bor gene clusters ), which are known to be activated when Mg ++ is limiting (65), as well as three of four genes under control of the Na + -dependent transcription factor NhaR (66,67). A set of genes involved in osmotic stress response (e.g., rrrD, psp, ybd, bet, aqp gene clusters and stress response sigma factor rpoE) (68)(69)(70)(71) were also upregulated in cells with condensates.…”