This Article Full Text Full Text (PDF) Supplemental material Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mercier, A. Articles by Labbé, S. Search for Related Content PubMed PubMed Citation Articles by Mercier, A. Articles by Labbé, S. Pubmed/NCBI databases Gene GEO Profiles HomoloGene Protein Compound via MeSH Substance via MeSH Hazardous Substances DB IRON

 Previous Article  |  Next Article 

Eukaryotic Cell, November 2006, p. 1866-1881, Vol. 5, No. 11
1535-9778/06/$08.00+0     doi:10.1128/EC.00199-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

A Transcription Factor Cascade Involving Fep1 and the CCAAT-Binding Factor Php4 Regulates Gene Expression in Response to Iron Deficiency in the Fission Yeast Schizosaccharomyces pombe ^,

Alexandre Mercier, Benoit Pelletier, and Simon Labbé^*

Département de Biochimie, Université de Sherbrooke, Sherbrooke, Québec J1H 5N4, Canada

Received 23 June 2006/ Accepted 31 August 2006

We have identified genes encoding candidate proteins involved in iron storage (pcl1⁺), the tricarboxylic acid cycle (sdh4⁺), and iron-sulfur cluster assembly (isa1⁺) that are negatively regulated in response to iron deprivation. Promoter deletion and site-directed mutagenesis permitted identification of a new cis-regulatory element in the promoter region of the pcl1⁺ gene. This cis-acting regulatory sequence containing the pentanucleotide sequence CCAAT is responsible for transcriptional repression of pcl1⁺ under low iron supply conditions. In Schizosaccharomyces pombe, the CCAAT-binding factor is a heteromeric DNA-binding complex that contains three subunits, designated Php2, Php3, and Php5. Inactivation of the php2⁺ locus negatively affects the transcriptional competency of pcl1⁺. A fourth subunit, designated Php4, is not essential for the transcriptional activation of target genes under basal and iron-replete conditions. We demonstrate that, in response to iron-limiting conditions, Php4 is required for down-regulation of pcl1⁺, sdh4⁺, and isa1⁺ mRNA levels. In vivo RNase protection studies reveal that the expression of php4⁺ is negatively regulated by iron and that this regulated expression requires a functional fep1⁺ gene. The results of these studies reveal that Fep1 represses php4⁺ expression in response to iron. In contrast, when iron is scarce, Fep1 becomes inactive and php4⁺ is expressed to act as a regulatory subunit of the CCAAT-binding factor that is required to block pcl1⁺, sdh4⁺, and isa1⁺ gene transcription.

---

* Corresponding author. Mailing address: Département de Biochimie, Faculté de Médecine, Université de Sherbrooke, 3001 12e Ave. Nord, Sherbrooke, Québec J1H 5N4, Canada. Phone: (819) 820-6868, ext. 15460. Fax: (819) 564-5340. E-mail: Simon.Labbe{at}USherbrooke.ca.

Published ahead of print on 8 September 2006.

Supplemental material for this article may be found at http://ec.asm.org/.

---

Eukaryotic Cell, November 2006, p. 1866-1881, Vol. 5, No. 11
1535-9778/06/$08.00+0     doi:10.1128/EC.00199-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Mercier, A., Labbe, S. (2009). Both Php4 Function and Subcellular Localization Are Regulated by Iron via a Multistep Mechanism Involving the Glutaredoxin Grx4 and the Exportin Crm1. J. Biol. Chem. 284: 20249-20262 [Abstract] [Full Text]  
• Steiner, W. W., Steiner, E. M., Girvin, A. R., Plewik, L. E. (2009). Novel Nucleotide Sequence Motifs That Produce Hotspots of Meiotic Recombination in Schizosaccharomyces pombe. Genetics 182: 459-469 [Abstract] [Full Text]  
• Jbel, M., Mercier, A., Pelletier, B., Beaudoin, J., Labbe, S. (2009). Iron Activates In Vivo DNA Binding of Schizosaccharomyces pombe Transcription Factor Fep1 through Its Amino-Terminal Region. Eukaryot Cell 8: 649-664 [Abstract] [Full Text]  
• Baek, Y.-U., Li, M., Davis, D. A. (2008). Candida albicans Ferric Reductases Are Differentially Regulated in Response to Distinct Forms of Iron Limitation by the Rim101 and CBF Transcription Factors. Eukaryot Cell 7: 1168-1179 [Abstract] [Full Text]  
• Mercier, A., Watt, S., Bahler, J., Labbe, S. (2008). Key Function for the CCAAT-Binding Factor Php4 To Regulate Gene Expression in Response to Iron Deficiency in Fission Yeast. Eukaryot Cell 7: 493-508 [Abstract] [Full Text]  
• Cuthbertson, B. J., Liao, Y., Birnbaumer, L., Blackshear, P. J. (2008). Characterization of zfs1 as an mRNA-binding and -destabilizing Protein in Schizosaccharomyces pombe. J. Biol. Chem. 283: 2586-2594 [Abstract] [Full Text]