Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of human cells treated with Bacillus anthracis lethal toxin (LT)-intoxicated HUVECs monolayers

ABSTRACT: We have analyzed the variation of transcriptome of HUVECs intoxicated by the lethal toxin of Bacillus anthracis at 4 and 8 hours Experiment Overall Design: Three experimental conditions with two biological replicates for the control condition corresponding to untreated HUVEC monolayer. RNA were extracted before labeling and hybridizations on Human U133A Plus 2.0 Affymetrix GeneChip

ORGANISM(S): Homo sapiens

SUBMITTER: emmanuel lemichez

PROVIDER: E-GEOD-12131 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Transcriptome dysregulation by anthrax lethal toxin plays a key role in induction of human endothelial cell cytotoxicity.

Rolando Monica M Stefani Caroline C Flatau Gilles G Auberger Patrick P Mettouchi Amel A Mhlanga Musa M Rapp Ulf U Galmiche Antoine A Lemichez Emmanuel E

Cellular microbiology 20100520 7

We have investigated how Bacillus anthracis lethal toxin (LT) triggers caspase-3 activation and the formation of thick actin cables in human endothelial cells. By DNA array analysis we show that LT has a major impact on the cell transcriptome and we identify key host genes involved in LT cytotoxic effects. Indeed, upregulation of TRAIL and downregulation of XIAP both participate in LT-induced caspase-3 activation. LT induces a downregulation of the immediate early gene and master regulator of tr ...[more]

PMID: 20088950

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Project description:Despite the scientific and applied interest in anaerobic metabolism of Saccharomyces cerevisiae, not all genes whose transcription is up-regulated under anaerobic conditions have yet been linked to known transcription factors. Experiments with a reporter construct in which the promoter of the anaerobically up-regulated TIR1 gene was fused to LacZ revealed a complete loss of anaerobic up-regulation in a snf7Δ mutant. Anaerobic up-regulation was restored by expression of a truncated allele of RIM101 that encodes for a constitutively active Rim101p transcription factor. Analysis of LacZ expression in several deletion mutants confirmed that the effect of Snf7p on anaerobic up-regulation of TIR1 involved Rim101p and did not require a functional multi-vesicular body sorting pathway (in which Snf7p also participates). Transcriptome analysis in anaerobic chemostat cultures revealed that 26 additional genes exhibited a Snf7p/Rim101p dependent anaerobic up-regulation. Since, in its activated form, Rim101p is generally known as a transcriptional repressor, its role in anaerobic up regulation of TIR1 and other ‘anaerobic’ yeast genes must involve additional factors. Further studies with deletion mutants in NRG1, NRG2 and SMP1, which were previously shown to be regulated by Rim101p, showed that these genes were not involved in the regulation of TIR1. However, the aerobic repression mechanism of TIR1 involved the general repressor Ssn6p-Tup1p complex. The physiological relevance of Snf7p/Rim101p-mediated transcriptional up-regulation of several genes in anaerobic yeast cultures was evident from reduced growth of a snf7Δ under anaerobic conditions. Experiment Overall Design: The aim of the present study is to investigate the role of SNF7 in the regulation of TIR1, to assess whether this role involves the Rim101p pathway, and to investigate whether Snf7p and/or Rim101p are also involved in regulation of other ‘anaerobic’ S. cerevisiae genes. After analyzing transcriptional regulation of TIR1 in several genetic backgrounds, a chemostat-based transcriptome analysis was performed on snf7Δ and rim101Δ strains as well as on the isogenic reference strain. Sets of genes that were differentially expressed in the snf7 and rim101 deletion strains were then compared to sets of genes that were previously shown to be transcriptionally up-regulated in anaerobic chemostat cultures of S. cerevisiae (Piper et al., 2002; Tai et al., 2005) Experiment Overall Design: Piper MD, Daran-Lapujade P, Bro C, Regenberg B, Knudsen S, Nielsen J & Pronk JT (2002) Reproducibility of oligonucleotide microarray transcriptome analyses. An interlaboratory comparison using chemostat cultures of Saccharomyces cerevisiae. J Biol Chem 277: 37001-37008. Experiment Overall Design: Tai SL, Boer VM, Daran-Lapujade P, Walsh MC, de Winde JH, Daran JM & Pronk JT (2005) Two-dimensional transcriptome analysis in chemostat cultures. Combinatorial effects of oxygen availability and macronutrient limitation in Saccharomyces cerevisiae. J Biol Chem 280: 437-447.

Dataset Information

Transcription profiling of human cells treated with Bacillus anthracis lethal toxin (LT)-intoxicated HUVECs monolayers

Publications

Transcriptome dysregulation by anthrax lethal toxin plays a key role in induction of human endothelial cell cytotoxicity.

Similar Datasets

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