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The propagation of perturbations in rewired bacterial gene networks.

ABSTRACT: 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.

SUBMITTER: Baumstark R

PROVIDER: S-EPMC4703840 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:This dataset contains transcription profiles of TOP10 E.coli transformed with 85 rewired network plasmids first described in: Evolvability and hierarchy in rewired bacterial gene networks. Nature 452:840-5 (2008). The data are described and analysed in an accompanying paper Baumstark et al.,The propagation of perturbations in shuffled bacterial gene networks (Submitted, 2015). 260 raw data microarrays are provided in total, representing biological triplicates (a,b and c; independent colonies grown from the same transformation, under standard growth conditions; LB, 16h). This is done for each of 255 promoter-ORF constructs (e.g. appY-crp, etc.) and 5 control construct microarrays (empty plasmid; Co). Co controls are provided for comparison, to show the relative effect of the rewiring genetic perturbation. The final processed data compares the number of perturbed genes, comparing between the average expression values of each rewired construct and Co. Methods: The 85 rewiring plasmids (Isalan et al, 2008) were transformed into E. coli TOP10 cells and grown under standardised conditions: bacteria were freshly plated onto LB Agar plates (with 100 μg/ml Ampicillin and 50 μg/ml Streptomycin) and incubated overnight at 37oC to form colonies. Single colonies (<3 days old) were used to inoculate 2 ml of LB in 14 ml culture tubes, containing 100 μg/ml Ampicillin and 50 μg/ml Streptomycin. Constructs were grown for 16h at 37oC, at 220 rpm in an orbital shaker. 10 μg of extracted total bacterial RNA (integrity number > 7.0) was used with Affymetrix GeneChip E. coli Genome 2.0 Arrays. Key to names: RAW DATA samples 1-260 _Co_1a.CEL = Control Co, colony a _Co_1b.CEL = Control Co, colony b etc. appY_O_30a.CEL = appY-promoter only, colony a appY_O_30b.CEL = appY-promoter only, colony b etc. appY_crp_34a.CEL = rewired construct, appY-promoter expressing crp ORF, colony a appY_crp_34b.CEL = rewired construct, appY-promoter expressing crp ORF, colony b appY_crp_34b.CEL = rewired construct, appY-promoter expressing crp ORF, colony c etc. PROCESSED DATA sample 261: probe_set_expression_value_norm_all - normalised data for all samples, for all E. coli K12 genes sample 262: probe_set_expression_value_norm_MG1655 - normalised data for all samples, for E. coli MG1655 subset of genes

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The propagation of perturbations in rewired bacterial gene networks.

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