Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Genome-wide dMTF-1-binding sites in Drosophila S2 cells in the absence or presence of copper or cadmium

ABSTRACT: Cells respond to changes in environment by shifting their gene expression profile to deal with the new conditions. The cellular response to changes in metal homeostasis is an important example of this. Transition metals such as iron, zinc, and copper are essential micronutrients but other metals such as cadmium are simply toxic. The cell must maintain metal concentrations in a window that supports efficient metabolic function but must also protect against the damaging effects of high concentrations of these metals. One way a cell regulates metal homeostasis is to control genes involved in metal mobilization and storage. Much of this regulation occurs at the level of transcription and the protein most responsible for this is the conserved metal responsive transcription factor, MTF-1. Interestingly, the nature of the changes in the gene expression profile depends on the type of exposure. The cell somehow senses the kind of metal challenge and responds appropriately. We have been using the Drosophila system to try to understand the mechanism of this metal discrimination. Using genome-wide mapping of MTF-1 binding under different metal stresses, we find that, surprisingly, MTF-1 chooses different DNA binding sites depending on the specific nature of the metal insult. We also find that the type of binding site chosen is an important component of the capability to induce the metal-specific transcription activation. Chromatin immunoprecipitation coupled with Drosophila genomic tiling arrays (ChIP-chip) was used to identify genomic regions directly bound by dMTF-1 in untreated and metal (Cu and Cd) challenged S2 cells. The dMTF-1 antibody was raised against amino acids 1-113 and 406-540 of MTF-1.

ORGANISM(S): Drosophila melanogaster

SUBMITTER: Hillel Sims

PROVIDER: E-GEOD-40535 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Background: The high number of heavy metal resistance genes in the soil bacterium Cupriavidus metallidurans CH34 makes it an interesting model organism to study microbial responses to heavy metals. Results: In this study the transcriptional response of this bacterium was measured after challenging it to a wide range of sub-lethal concentrations of various essential or toxic metals. Considering the global transcriptional responses for each challenge as well as by identifying the overlap in upregulated genes between different metal responses, the sixteen metals could be clustered in three different groups. Additionally, next to the assessment of the transcriptional response of already known metal resistance genes, new metal response gene clusters were identified. The majority of the metal response loci showed similar expression profiles when cells were exposed to different metals, suggesting complex cross-talk at transcriptional level between the different metal responses. The highly redundant nature of these metal resistant regions – illustrated by the large number of paralogous genes – combined with the phylogenetic distribution of these metal response regions within evolutionary related and other metal resistant bacteria, provides important insights on the recent evolution of this naturally soil dwelling bacterium towards a highly metal-resistant strain found in harsh and anthropogenic environments. Conclusions: The metal-resistant soil bacterium Cupriavidus metallidurans CH34 displays myriads of gene expression patterns when exposed to a wide range of heavy metals at non-lethal concentrations. The interplay between the different gene expression clusters points towards a complex cross-regulated regulatory network governing heavy metal resistance in C. metallidurans CH34. Keywords: Cupriavidus metallidurans CH34, transcriptional regulation, heavy metal resistance Two-condition experiments. Comparing samples after induction with heavy metals versus non-induced samples. Biological duplicate or triplicate. Each array contains 3 or 4 technical replicates.

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Genome-wide dMTF-1-binding sites in Drosophila S2 cells in the absence or presence of copper or cadmium

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