What happens to gene expression when you add new links to a gene regulatory network? To answer this question, we profile 85 network rewirings in E. coli. Here we report that concerted patterns of differential expression propagate from reconnected hub genes. The rewirings link promoter regions to different transcription factor and σ-factor genes, resulting in perturbations that span four orders of magnitude, changing up to ∼70% of the transcriptome. Importantly, factor connectivity and promoter activity both associate with perturbation size. Perturbations from related rewirings have more similar transcription profiles and a statistical analysis reveals ∼20 underlying states of the system, associating particular gene groups with rewiring constructs. We examine two large clusters (ribosomal and flagellar genes) in detail. These represent alternative global outcomes from different rewirings because of antagonism between these major cell states. This data set of systematically related perturbations enables reverse engineering and discovery of underlying network interactions.

Funding was provided by FP7 ERC 201249 ZINC-HUBS (R.B.), Spanish grants MICINNBFU2010-17953 (M.I.), MINECO TIN2011-22826 (R.C., S.H.), ISCIII COMBIOMEDRD07/0067/0001 (R.C., S.H.). Y.S. was funded by a Swiss National Science FoundationFellowship (PBSKP3_134331/1) and by the Marie Curie Action (FP7 PIEF-GA-2011-298348). M.I. was funded by New Investigator Award No. WT102944 from theWellcome Trust UK