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The Impact of Global Transcriptional Regulation on Bacterial Gene Order.

ABSTRACT: Bacterial gene expression depends on the allocation of limited transcriptional resources provided a particular growth rate and growth condition. Early studies in a few genes suggested this global regulation to generate a unifying hyperbolic expression pattern. Here, we developed a large-scale method that generalizes these experiments to quantify the response to growth of over 700 genes that a priori do not exhibit any specific control. We distinguish a core subset following a promoter-specific hyperbolic response. Within this group, we sort genes with regard to their responsiveness to the global regulatory program to show that those with a particularly sensitive linear response are located near the origin of replication. We then find evidence that this genomic architecture is biologically significant by examining position conservation of E. coli genes in 100 bacteria. The response to the transcriptional resources of the cell results in an additional feature contributing to bacterial genome organization.

SUBMITTER: Yubero P

PROVIDER: S-EPMC7155222 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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The Impact of Global Transcriptional Regulation on Bacterial Gene Order.

Yubero Pablo P Poyatos Juan F JF

iScience 20200402 4

Bacterial gene expression depends on the allocation of limited transcriptional resources provided a particular growth rate and growth condition. Early studies in a few genes suggested this global regulation to generate a unifying hyperbolic expression pattern. Here, we developed a large-scale method that generalizes these experiments to quantify the response to growth of over 700 genes that a priori do not exhibit any specific control. We distinguish a core subset following a promoter-specific h ...[more]

PMID: 32283521

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Project description:Genetic variants altering cis-regulation of normal gene expression (cis-eQTLs) have been extensively mapped in human cells and tissues, but the extent by which controlled, environmental perturbation influences cis-eQTLs is unclear. We carried out large-scale induction experiments using primary human bone cells derived from unrelated donors of Swedish origin treated with 18 different stimuli (7 treatments and 2 controls, each assessed at 2 time points). The treatments with the largest impact on the transcriptome, verified on two independent expression arrays, included BMP-2 (t?=?2h), dexamethasone (DEX) (t?=?24 h), and PGE? (t?=?24 h). Using these treatments and control, we performed expression profiling for 18,144 RefSeq transcripts on biological replicates of the complete study cohort of 113 individuals (n(total)?=?782) and combined it with genome-wide SNP-genotyping data in order to map treatment-specific cis-eQTLs (defined as SNPs located within the gene ± 250 kb). We found that 93% of cis-eQTLs at 1% FDR were observed in at least one additional treatment, and in fact, on average, only 1.4% of the cis-eQTLs were considered as treatment-specific at high confidence. The relative invariability of cis-regulation following perturbation was reiterated independently by genome-wide allelic expression tests where only a small proportion of variance could be attributed to treatment. Treatment-specific cis-regulatory effects were, however, 2- to 6-fold more abundant among differently expressed genes upon treatment. We further followed-up and validated the DEX-specific cis-regulation of the MYO6 and TNC loci and found top cis-regulatory variants located 180 kb and 250 kb upstream of the transcription start sites, respectively. Our results suggest that, as opposed to tissue-specificity of cis-eQTLs, the interactions between cellular environment and cis-variants are relatively rare (?1.5%), but that detection of such specific interactions can be achieved by a combination of functional genomic approaches as described here.

Dataset Information

The Impact of Global Transcriptional Regulation on Bacterial Gene Order.

Publications

The Impact of Global Transcriptional Regulation on Bacterial Gene Order.

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