Aft1p and Aft2p Mediate Iron-responsive Gene Expression in Yeast through Related Promoter Elements*

The transcription factors Aft1p and Aft2p from Saccharomyces cerevisiae regulate the expression of genes that are involved in iron homeostasis. In vitro studies have shown that both transcription factors bind to an iron-responsive element (FeRE) that is present in the upstream region of genes in the iron regulon. We have used DNA microarrays to distinguish the genes that are activated by Aft1p and Aft2p and to establish for the first time that each factor gives rise to a unique transcriptional profile due to the differential expression of individual iron-regulated genes. We also show that both Aft1p and Aft2p mediate the in vivo expression of FET3 and FIT3 through a consensus FeRE. In addition, both proteins regulate MRS4 via a variant FeRE with Aft2p being the stronger activator from this particular element. Like other paralogous pairs of transcription factors within S. cerevisiae, Aft1p and Aft2p are able to interact with the same promoter elements while maintaining specificity of gene activation.

[1]  K. Struhl,et al.  Yap, a novel family of eight bZIP proteins in Saccharomyces cerevisiae with distinct biological functions , 1997, Molecular and cellular biology.

[2]  P. Blaiseau,et al.  Aft2p, a Novel Iron-regulated Transcription Activator That Modulates, with Aft1p, Intracellular Iron Use and Resistance to Oxidative Stress in Yeast* , 2001, The Journal of Biological Chemistry.

[3]  D. Stillman,et al.  Role of negative regulation in promoter specificity of the homologous transcriptional activators Ace2p and Swi5p , 1996, Molecular and cellular biology.

[4]  D. Kinney,et al.  Yeast shuttle and integrative vectors with multiple cloning sites suitable for construction of lacZ fusions. , 1986, Gene.

[5]  Yuko Yamaguchi-Iwai,et al.  Subcellular Localization of Aft1 Transcription Factor Responds to Iron Status in Saccharomyces cerevisiae * , 2002, The Journal of Biological Chemistry.

[6]  F. Foury,et al.  Mitochondrial Control of Iron Homeostasis , 2001, The Journal of Biological Chemistry.

[7]  W. H. Mager,et al.  Different roles for abf1p and a T-rich promoter element in nucleosome organization of the yeast RPS28A gene. , 2000, Nucleic acids research.

[8]  Liangtao Li,et al.  The Yeast Gene MSC2, a Member of the Cation Diffusion Facilitator Family, Affects the Cellular Distribution of Zinc* , 2001, The Journal of Biological Chemistry.

[9]  G. Church,et al.  Discrimination between paralogs using microarray analysis: application to the Yap1p and Yap2p transcriptional networks. , 2002, Molecular biology of the cell.

[10]  D. Winge,et al.  Metalloregulation of FRE1 and FRE2Homologs in Saccharomyces cerevisiae * , 1998, The Journal of Biological Chemistry.

[11]  Rudy Pandjaitan,et al.  The yeast zinc finger regulators Pdr1p and Pdr3p control pleiotropic drug resistance (PDR) as homo‐ and heterodimers in vivo , 2002, Molecular microbiology.

[12]  R. Klausner,et al.  Iron‐regulated DNA binding by the AFT1 protein controls the iron regulon in yeast. , 1996, The EMBO journal.

[13]  M Aldea,et al.  The AFT1 Transcriptional Factor is Differentially Required for Expression of High‐Affinity Iron Uptake Genes in Saccharomyces cerevisiae , 1997, Yeast.

[14]  F. Foury,et al.  Deletion of the Mitochondrial Carrier Genes MRS3 andMRS4 Suppresses Mitochondrial Iron Accumulation in a Yeast Frataxin-deficient Strain* , 2002, The Journal of Biological Chemistry.

[15]  R. Schweyen,et al.  The Yeast Iron Regulon Is Induced upon Cobalt Stress and Crucial for Cobalt Tolerance* , 2002, The Journal of Biological Chemistry.

[16]  D Botstein,et al.  Three Cell Wall Mannoproteins Facilitate the Uptake of Iron in Saccharomyces cerevisiae * , 2001, The Journal of Biological Chemistry.

[17]  Nicola J. Rinaldi,et al.  Transcriptional Regulatory Networks in Saccharomyces cerevisiae , 2002, Science.

[18]  S. Dorland,et al.  Parallel pathways of gene regulation: homologous regulators SWI5 and ACE2 differentially control transcription of HO and chitinase. , 1992, Genes & development.

[19]  L. Johnston,et al.  Rme1, a negative regulator of meiosis, is also a positive activator of G1 cyclin gene expression. , 1995, The EMBO journal.

[20]  C. Yun,et al.  Siderophore-Iron Uptake in Saccharomyces cerevisiae , 2000, The Journal of Biological Chemistry.

[21]  S. Henry,et al.  Functional Characterization of an Inositol-sensitive Upstream Activation Sequence in Yeast , 1995, The Journal of Biological Chemistry.

[22]  D. Botstein,et al.  Genomic expression programs in the response of yeast cells to environmental changes. , 2000, Molecular biology of the cell.

[23]  M. Portnoy,et al.  The distinct methods by which manganese and iron regulate the Nramp transporters in yeast. , 2002, The Biochemical journal.

[24]  P. Brown,et al.  A second iron-regulatory system in yeast independent of Aft1p , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[25]  M. Gerstein,et al.  Subcellular localization of the yeast proteome. , 2002, Genes & development.

[26]  George M. Church,et al.  Regulatory Networks Revealed by Transcriptional Profiling of Damaged Saccharomyces cerevisiae Cells: Rpn4 Links Base Excision Repair with Proteasomes , 2000, Molecular and Cellular Biology.

[27]  D Botstein,et al.  Desferrioxamine-mediated Iron Uptake in Saccharomyces cerevisiae , 2000, The Journal of Biological Chemistry.

[28]  L. Johnston,et al.  Overlapping and distinct roles of the duplicated yeast transcription factors Ace2p and Swi5p , 2001, Molecular microbiology.

[29]  J. Kaplan,et al.  Inhibition of Fe-S cluster biosynthesis decreases mitochondrial iron export: Evidence that Yfh1p affects Fe-S cluster synthesis , 2002, Proceedings of the National Academy of Sciences of the United States of America.