title: Php4 Is a Key Player for Iron Economy in Meiotic and Sporulating Cells.
abstract: Meiosis is essential for sexually reproducing organisms, including the fission yeast Schizosaccharomyces pombe In meiosis, chromosomes replicate once in a diploid precursor cell (zygote), and then segregate twice to generate four haploid meiotic products, named spores in yeast. In S. pombe, Php4 is responsible for the transcriptional repression capability of the heteromeric CCAAT-binding factor to negatively regulate genes encoding iron-using proteins under low-iron conditions. Here, we show that the CCAAT-regulatory subunit Php4 is required for normal progression of meiosis under iron-limiting conditions. Cells lacking Php4 exhibit a meiotic arrest at metaphase I. Microscopic analyses of cells expressing functional GFP-Php4 show that it colocalizes with chromosomal material at every stage of meiosis under low concentrations of iron. In contrast, GFP-Php4 fluorescence signal is lost when cells undergo meiosis under iron-replete conditions. Global gene expression analysis of meiotic cells using DNA microarrays identified 137 genes that are regulated in an iron- and Php4-dependent manner. Among them, 18 genes are expressed exclusively during meiosis and constitute new putative Php4 target genes, which include hry1+and mug14+Further analysis validates that Php4 is required for maximal and timely repression of hry1+and mug14+genes. Using a chromatin immunoprecipitation approach, we show that Php4 specifically associates with hry1+and mug14+promoters in vivo Taken together, the results reveal that in iron-starved meiotic cells, Php4 is essential for completion of the meiotic program since it participates in global gene expression reprogramming to optimize the use of limited available iron.
authors.affiliation: Département de Biochimie, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Quebec, J1E 4K8, Canada.
authors.forename: Ariane
authors.initials: A
authors.lastname: Brault
authors.affiliation: Research Department of Genetics, Evolution and Environment, University College London, WC1E 6BT, UK.
authors.forename: Charalampos
authors.initials: C
authors.lastname: Rallis
authors.affiliation: Département de Biochimie, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Quebec, J1E 4K8, Canada.
authors.forename: Vincent
authors.initials: V
authors.lastname: Normant
authors.affiliation: Département de Biochimie, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Quebec, J1E 4K8, Canada.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Garant
authors.affiliation: Research Department of Genetics, Evolution and Environment, University College London, WC1E 6BT, UK.
authors.forename: Jürg
authors.initials: J
authors.lastname: Bähler
authors.affiliation: Département de Biochimie, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Quebec, J1E 4K8, Canada Simon.Labbe@USherbrooke.ca.
authors.forename: Simon
authors.initials: S
authors.lastname: Labbé
mesh_terms: D000483:Alleles; D023081:CCAAT-Binding Factor / Q000235:genetics* / Q000378:metabolism*; D059447:Cell Cycle Checkpoints / Q000235:genetics; D020869:Gene Expression Profiling; D007501:Iron / Q000378:metabolism*; D008540:Meiosis / Q000235:genetics*; D008677:Metaphase / Q000235:genetics; D009154:Mutation; D009584:Nitrogen / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D021381:Protein Transport; D012568:Schizosaccharomyces / Q000235:genetics* / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics* / Q000378:metabolism*; D013312:Stress, Physiological / Q000235:genetics; D059467:Transcriptome
chemical_list: D023081:CCAAT-Binding Factor; C519990:Php4 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; D007501:Iron; D009584:Nitrogen
keywords: CCAAT-binding factor; fission yeast; iron-regulated genes; iron-sparing response; meiosis