Inhibition of Heme Biosynthesis Prevents Transcription of Iron Uptake Genes in Yeast
| Autor: | Annette Pollington, Shulamit Jaron, Charles A. Galea, Robert J. Crisp, Yuko Yamaguchi-Iwai, Jerry Kaplan |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Transcriptional Activation
Saccharomyces cerevisiae Proteins Time Factors Transcription Genetic Iron Green Fluorescent Proteins Saccharomyces cerevisiae Heme Biochemistry chemistry.chemical_compound Cytosol Genes Reporter Transcription (biology) Promoter Regions Genetic Molecular Biology Alleles Cell Nucleus biology Single-Strand Specific DNA and RNA Endonucleases Cell Biology Metabolism beta-Galactosidase biology.organism_classification Precipitin Tests Chromatin Yeast Mitochondria Oxygen Luminescent Proteins Zinc Regulon chemistry Chromatin immunoprecipitation Copper Plasmids Transcription Factors |
| Zdroj: | Journal of Biological Chemistry. 278:45499-45506 |
| ISSN: | 0021-9258 |
| Popis: | Yeast are capable of modifying their metabolism in response to environmental changes. We investigated the activity of the oxygen-dependent high-affinity iron uptake system of Saccharomyces cerevisiae under conditions of heme depletion. We found that the absence of heme, due to a deletion in the gene that encodes delta-aminolevulinic acid synthase (HEM1), resulted in decreased transcription of genes belonging to both the iron and copper regulons, but not the zinc regulon. Decreased transcription of the iron regulon was not due to decreased expression of the iron sensitive transcriptional activator Aft1p. Expression of the constitutively active allele AFT1-1up was unable to induce transcription of the high affinity iron uptake system in heme-depleted cells. We demonstrated that under heme-depleted conditions, Aft1p-GFP was able to cycle normally between the nucleus and cytosol in response to cytosolic iron. Despite the inability to induce transcription under low iron conditions, chromatin immunoprecipitation demonstrated that Aft1p binds to the FET3 promoter in the absence of heme. Finally, we provide evidence that under heme-depleted conditions, yeast are able to regulate mitochondrial iron uptake and do not accumulate pathologic iron concentrations, as is seen when iron-sulfur cluster synthesis is disrupted. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|