Fep1 represses expression of the fission yeast Schizosaccharomyces pombe siderophore-iron transport system

Abstract

When iron repletes, Schizosaccharomyces pombe cells repress transcription of genes encoding components involved in the reductive iron transport system. Fep1 mediates this transcriptional control by interacting specifically with GATA-type cis-acting elements. To further investigate the role that Fep1 plays in iron homeostasis, we searched for additional Fep1-regulated genes. We found that str1+ is subject to negative transcriptional regulation, which is exerted through binding of Fep1 to a single GATA element in the str1+ promoter. Introduction of str1+ into a Saccharomyces cerevisiae fet3Delta arn1-4Delta strain led to assimilation of iron from ferrichrome, revealing that Str1 functions as a siderophore-iron transporter in S.pombe. We also identified two additional target genes of Fep1, named str2+ and str3+. We demonstrate that the str1+, str2+ and str3+ genes share a common promoter element, 5'-(A/T)GATAA-3'. We found that the N-terminal 241 residue segment of Fep1 expressed in Escherichia coli specifically interacts with the 5'-(A/T)GATAA-3' element present in each of these promoters. Consistent with this, constitutive high level str1+, str2+ and str3+ gene expression was observed in a fep1Delta mutant strain. Taken together, these results demonstrate that Fep1 occupies a central role in coordinating transcriptional regulation of genes encoding components of the reductive and non-reductive iron transport systems in fission yeast.

An Iron Enhancer Element in the FTN-1 Gene Directs Iron-dependent Expression in Caenorhabditis elegans Intestine

“…One model proposes that ELT-2 itself is regulated by iron. GATA proteins have been shown to regulate the transcription of iron transport genes in Schizosaccharomyces pombe (36) and siderophore synthesis genes in Neurospora crassa (35), Ustilage maydis (37) and Aspergillus nidulans (53) during iron-sufficient conditions. In S. pombe, the GATA factor Fep1 binds DNA in the presence of iron and recruits the co-repressors Tup11 and Tup12, leading to the transcriptional inactivation of iron transport genes (54).…”

Both Php4 Function and Subcellular Localization Are Regulated by Iron via a Multistep Mechanism Involving the Glutaredoxin Grx4 and the Exportin Crm1

“…When iron levels are high, Fep1 binds to GATA cis-acting elements found in the promoter regions of genes involved in iron acquisition (e.g. fip1 ϩ , fio1 ϩ , frp1 ϩ , and str1 ϩ /2 ϩ /3 ϩ ) and shuts down their expression to avoid deleterious consequences of iron overload (6,7). When iron levels are low, Fep1 is unable to bind DNA, resulting in the transcriptional induction of genes involved in iron acquisition (6,8,9).…”

Functional Comparison of the Tup11 and Tup12 Transcriptional Corepressors in Fission Yeast

“…The fission yeast is unusual compared to other fungi because it contains two genes encoding Tup1-like corepressors. Evidence that the S. pombe proteins function similarly to the Tup1-Ssn6 complex in S. cerevisiae has been reported recently (12,14,16,23,24,27,45). Tup11 has been shown to repress target genes containing LexA binding sites when fused to the LexA DNAbinding domain, and binding studies have shown that Tup11 is able to interact with the S. cerevisiae transcription factor Mat␣2 (24).…”