Single nucleotide in the MTF-1 binding site can determine metal-specific transcription activation
| Autor: | Gung-wei Chirn, Michael T. Marr, Hillel I. Sims |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Transcriptional Activation
Blotting Western Gene Expression Plasma protein binding Biology Response Elements DNA-binding protein Cell Line Transcription (biology) Gene expression Animals Drosophila Proteins Immunoprecipitation Point Mutation Nucleotide Motifs Binding site Promoter Regions Genetic Cation Transport Proteins Gene Transcription factor Copper Transporter 1 Oligonucleotide Array Sequence Analysis Genetics Binding Sites Multidisciplinary Base Sequence Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling Biological Sciences Cell biology DNA-Binding Proteins DNA binding site Drosophila melanogaster Metals Metallothionein Copper Cadmium Protein Binding Transcription Factors |
| Zdroj: | Proceedings of the National Academy of Sciences. 109:16516-16521 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1207737109 |
| Popis: | 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 1 (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 the 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. |
| Databáze: | OpenAIRE |
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