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. 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. Saccharomyces cerevisiae contains paralogous gene pairs that code for transcription factors that can have both overlapping and distinct functions. These transcription factors bind to the same promoter elements but generate distinct transcriptional profiles. Included in this group are Ace2p/Swi5p, Pdr1p/Pdr3p, and Yap1/Yap2p. Ace2p and Swi5p regulate the expression of cell cycle-specific genes, are 83% identical in their zinc finger DNA-binding domains and recognize the same DNA binding site in vitro (1Dohrmann P.R. Butler G. Tamai K. Dorland S. Greene J.R. Thiele D.J. Stillman D.J. Genes Dev. 1992; 6: 93-104Crossref PubMed Scopus (176) Google Scholar, 2Dohrmann P.R. Voth W.P. Stillman D.J. Mol. Cell. Biol. 1996; 16: 1746-1758Crossref PubMed Scopus (66) Google Scholar). However, Ace2p and Swi5p can regulate separate genes, where discrimination between promoter elements is achieved through the interaction of these factors with other DNA-binding proteins (2Dohrmann P.R. Voth W.P. Stillman D.J. Mol. Cell. Biol. 1996; 16: 1746-1758Crossref PubMed Scopus (66) Google Scholar). Alternatively, in cases where both transcription factors can induce the expression of the same gene, one is often the more potent activator (3Toone W.M. Johnson A.L. Banks G.R. Toyn J.H. Stuart D. Wittenberg C. Johnston L.H. EMBO J. 1995; 14: 5824-5832Crossref PubMed Scopus (57) Google Scholar). There are genes that require both Ace2p and Swi5p for maximal expression and others that are antagonistically regulated by these factors (4Doolin M.T. Johnson A.L. Johnston L.H. Butler G. Mol. Microbiol. 2001; 40: 422-432Crossref PubMed Scopus (109) Google Scholar). Pdr1p and Pdr3p share 36% identity and regulate the expression of genes that are involved in pleiotropic drug resistance. Both these factors are able to bind to the same DNA element (PDRE) in vivo as either hetero- or homodimers (5Mamnun Y.M. Pandjaitan R. Mahe Y. Delahodde A. Kuchler K. Mol. Microbiol. 2002; 46: 1429-1440Crossref PubMed Scopus (98) Google Scholar). Differential expression of Pdr1p/Pdr3p target genes may therefore involve different combinations of Pdr1p/Pdr3p at different PDREs (5Mamnun Y.M. Pandjaitan R. Mahe Y. Delahodde A. Kuchler K. Mol. Microbiol. 2002; 46: 1429-1440Crossref PubMed Scopus (98) Google Scholar). Yap1p and Yap2p are 88% identical in their DNA binding regions and bind to the same consensus site (6Fernandes L. Rodrigues-Pousada C. Struhl K. Mol. Biol. Cell. 1997; 17: 6982-6993Crossref Scopus (262) Google Scholar). Analysis of global gene expression using microarrays has shown that although Yap1p and Yap2p are both involved in the response to cellular stresses, they regulate different regulons (7Cohen B.A. Pilpel Y. Mitra R.D. Church G.M. Mol. Biol. Cell. 2002; 13: 1608-1614Crossref PubMed Scopus (54) Google Scholar). The mechanism(s) of Yap1p/Yap2p gene selectivity are not understood but may include variations in the base pairs flanking the consensus Yap binding site (7Cohen B.A. Pilpel Y. Mitra R.D. Church G.M. Mol. Biol. Cell. 2002; 13: 1608-1614Crossref PubMed Scopus (54) Google Scholar). The iron regulon of S. cerevisiae is well characterized and includes genes that are involved in the uptake, compartmentalization and use of iron. These include genes that encode siderophore transporters (ARN1–4), iron reductases (FRE1–6), iron permeases (FTR1, FET4), and multicopper oxidases that are involved in the coordinated oxidation and transport of iron across membranes (FET3, FET5) (8Martins L. Jensen L.T. Simon J.R. Keller G. Winge D.R. J. Biol. Chem. 1997; 273: 23716-23721Abstract Full Text Full Text PDF Scopus (169) Google Scholar, 9Dancis A. J. Pediatr. 1998; 12: S24-S29Abstract Full Text Full Text PDF Google Scholar, 10Yun C.-W. Ferea T. Rashford J. Ardon O. Brown P.O. Botstein D. Kaplan J. Philpott C.C. J. Biol. Chem. 2000; 275: 10709-10715Abstract Full Text Full Text PDF PubMed Scopus (165) Google Scholar, 11Yun C.-W. Tiedeman J.S. Moore R.E. Philpott C.C. J. Biol. Chem. 2000; 275: 16354-16359Abstract Full Text Full Text PDF PubMed Scopus (129) Google Scholar, 12Foury F. Talibi D. J. Biol. Chem. 2001; 276: 7762-7768Abstract Full Text Full Text PDF PubMed Scopus (161) Google Scholar). In addition, three related genes (FIT1-FIT3) encode proteins that localize within the yeast cell wall and whose function is partially related to siderophore uptake (13Protchenko O. Ferea T. Rashford J. Tiedeman J. Brown P.O. Botstein D. Philpott C.C. J. Biol. Chem. 2001; 276: 49244-49250Abstract Full Text Full Text PDF PubMed Scopus (134) Google Scholar). Genes within the iron regulon are induced under low iron conditions and are regulated by the transcription factors, Aft1p and Aft2p (14Yamaguchi-iwai Y. Stearman R. Dancis A. Klausner D. EMBO J. 1996; 15: 3377-3384Crossref PubMed Scopus (292) Google Scholar, 15Rutherford J.C. Jaron S. Ray E. Brown P.O. Winge D.R. Proc. Natl. Acad. Sci. U. S. A. 2001; 98: 14322-14327Crossref PubMed Scopus (129) Google Scholar, 18Blaiseau P.-L. E. J. Biol. Chem. 2001; 276: Full Text Full Text PDF PubMed Scopus Google Scholar). Aft1p and Aft2p are identical within their the DNA binding of each J.C. Jaron S. Ray E. Brown P.O. Winge D.R. Proc. Natl. Acad. Sci. U. S. A. 2001; 98: 14322-14327Crossref PubMed Scopus (129) Google Scholar). The of Aft1p is within to the DNA binding transcription in an Y. R. A. R. J. Biol. Chem. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar). In addition, the region of Aft1p contains a that differential cellular of Aft1p in response to iron Y. R. A. R. J. Biol. Chem. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar). Aft1p is to the under but is and in of and and have that in the of the iron regulon (14Yamaguchi-iwai Y. Stearman R. Dancis A. Klausner D. EMBO J. 1996; 15: 3377-3384Crossref PubMed Scopus (292) Google Scholar, 15Rutherford J.C. Jaron S. Ray E. Brown P.O. Winge D.R. Proc. Natl. Acad. Sci. U. S. A. 2001; 98: 14322-14327Crossref PubMed Scopus (129) Google Scholar). These of function from a to in identical regions of Aft1p and that a Aft1p in conditions and iron uptake and cell (14Yamaguchi-iwai Y. Stearman R. Dancis A. Klausner D. EMBO J. 1996; 15: 3377-3384Crossref PubMed Scopus (292) Google Scholar, C. C. C. R. E. 1997; 13: PubMed Scopus Google Scholar). The is able to partially iron uptake in the J.C. Jaron S. Ray E. Brown P.O. Winge D.R. Proc. Natl. Acad. Sci. U. S. A. 2001; 98: 14322-14327Crossref PubMed Scopus (129) Google Scholar). The has J.C. Jaron S. Ray E. Brown P.O. Winge D.R. Proc. Natl. Acad. Sci. U. S. A. 2001; 98: 14322-14327Crossref PubMed Scopus (129) Google Scholar). However, the is more to conditions the J.C. Jaron S. Ray E. Brown P.O. Winge D.R. Proc. Natl. Acad. Sci. U. S. A. 2001; 98: 14322-14327Crossref PubMed Scopus (129) Google Scholar, 18Blaiseau P.-L. E. J. Biol. Chem. 2001; 276: Full Text Full Text PDF PubMed Scopus Google Scholar). The also to with as a and this is partially by with low the or J.C. Jaron S. Ray E. Brown P.O. Winge D.R. Proc. Natl. Acad. Sci. U. S. A. 2001; 98: 14322-14327Crossref PubMed Scopus (129) Google Scholar). Analysis of global gene expression has shown that the the expression of a of the iron regulon J.C. Jaron S. Ray E. Brown P.O. Winge D.R. Proc. Natl. Acad. Sci. U. S. A. 2001; 98: 14322-14327Crossref PubMed Scopus (129) Google Scholar). However, not for both and the and the regulate the expression of iron-regulated genes and J.C. Jaron S. Ray E. Brown P.O. Winge D.R. Proc. Natl. Acad. Sci. U. S. A. 2001; 98: 14322-14327Crossref PubMed Scopus (129) Google Scholar). Aft1p transcriptional through an iron-responsive element (FeRE) used iron-responsive upstream that has the consensus (14Yamaguchi-iwai Y. Stearman R. Dancis A. Klausner D. EMBO J. 1996; 15: 3377-3384Crossref PubMed Scopus (292) Google Scholar). The FeRE by the in vivo of the FET3 promoter region using and DNA (14Yamaguchi-iwai Y. Stearman R. Dancis A. Klausner D. EMBO J. 1996; 15: 3377-3384Crossref PubMed Scopus (292) Google Scholar). Aft1p to the FET3 FeRE in vivo in an to the FET3 FeRE in the promoter regions of other iron-regulated genes. In vitro the binding of Aft1p to these particular from the consensus FeRE (14Yamaguchi-iwai Y. Stearman R. Dancis A. Klausner D. EMBO J. 1996; 15: 3377-3384Crossref PubMed Scopus (292) Google Scholar). that a is also iron-regulated in an through a consensus FeRE Jensen L.T. J. 2002; PubMed Scopus Google Scholar). of Aft1p and Aft2p bind to the FET3 FeRE in with both factors the iron regulon through the consensus FeRE J.C. Jaron S. Ray E. Brown P.O. Winge D.R. Proc. Natl. Acad. Sci. U. S. A. 2001; 98: 14322-14327Crossref PubMed Scopus (129) Google Scholar). of from a but not the of the expression of a under the of the FET3 FeRE in an P.-L. E. J. Biol. Chem. 2001; 276: Full Text Full Text PDF PubMed Scopus Google Scholar). However, the expression of one of a of transcription factors can in the of genes that are regulated by the other factor (2Dohrmann P.R. Voth W.P. Stillman D.J. Mol. Cell. Biol. 1996; 16: 1746-1758Crossref PubMed Scopus (66) Google Scholar). is therefore not to Aft1p and Aft2p interact with the same element in The is therefore with Aft1p and Aft2p overlapping but in the transcriptional of the iron regulon in S. We are in the of this iron-responsive transcription In this have used to the of the of function and that they rise to different global transcriptional profiles. We have also the of Aft1p and Aft2p to transcription through the same consensus FeRE. In vivo show that Aft1p and Aft2p gene expression through the consensus in the FET3 and FIT3 promoter Both Aft1p and Aft2p also induce the of MRS4 through a variant FeRE. FeRE has that is in the genes that are induced by the and and the of the and from a of the at the by a with that using and for The of the and the of the at the using and DNA with as a in yeast and and are of and J.C. Jaron S. Ray E. Brown P.O. Winge D.R. Proc. Natl. Acad. Sci. U. S. A. 2001; 98: 14322-14327Crossref PubMed Scopus (129) Google from the and have the the of function of and within and are under the of their J.C. Jaron S. Ray E. Brown P.O. Winge D.R. Proc. Natl. Acad. Sci. U. S. A. 2001; 98: 14322-14327Crossref PubMed Scopus (129) Google Scholar). The by the from the The and a from Dancis (14Yamaguchi-iwai Y. Stearman R. Dancis A. Klausner D. EMBO J. 1996; 15: 3377-3384Crossref PubMed Scopus (292) Google Scholar). These a and of the FET3 FeRE in a The of the of of the to the gene in A. PubMed Scopus Google a from Kaplan L. Kaplan J. J. Biol. Chem. 2001; 276: Full Text Full Text PDF PubMed Scopus Google Scholar). generate a of in the same FeRE that is present in to a FeRE to used as for using the and to generate The the FET3 from and and the of to generate and generate of of of the to the gene in DNA from and used as for using the and The the of to generate used as for using the and to to to and generate The FIT3 from both and and to the of to generate and generate of of of the to the gene in DNA from used as for using the and The the of to generate used as for using and to generate of the MRS4 promoter The and the from the of to generate used as for using the and and and to and that to in individual generate a that contains the FeRE of MRS4 within the promoter to the gene, of each of the overlapping and in for and at The the of J. Biol. Chem. 1995; Full Text Full Text PDF PubMed Scopus Google to generate by DNA yeast using the In the of using in under and with by used for of with or at and using the R. R.E. Moore Struhl K. in Scholar). DNA with to FIT3 and as an with using as (1Dohrmann P.R. Butler G. Tamai K. Dorland S. Greene J.R. Thiele D.J. Stillman D.J. Genes Dev. 1992; 6: 93-104Crossref PubMed Scopus (176) Google Scholar). the with of in at The with of and the and in The using an with and their as in of and at an of by the and from using the the used to generate by transcription with of or The as The of the S. cerevisiae from and The not to and in using a The an and with a using The of by the for genes, and the for three The to that not the and Analysis of the within the induced genes using the The the and are as Analysis of Aft1p and Aft2p studies have shown that Aft1p and Aft2p the expression of a of the iron-regulated genes in S. cerevisiae J.C. Jaron S. Ray E. Brown P.O. Winge D.R. Proc. Natl. Acad. Sci. U. S. A. 2001; 98: 14322-14327Crossref PubMed Scopus (129) Google Scholar). We to the of Aft1p and Aft2p global gene expression in of the same DNA to the expression profile from the the The used and The from their in low as to the of the of function The transcriptional of the and the with that of three The for each gene and the genes that induced in the and and These include genes that are the of Aft1p Aft2p or genes that are activated as the of the of can in the induced by not not in a induced by not not in a of the genes as being induced as the of the are to code for proteins that are involved in iron of these genes are induced to a as the of either Aft1p or Aft2p However, the more induced genes to activated to a Aft1p is present There are of genes that a consensus FeRE but are induced as the of one of the These genes include the and and the and for a with to and is involved in cell wall although function is not Included in the group of genes that are induced as the of Aft1p is is within a region of that contains a group of genes that are induced in either or for a that identity with the from S. cerevisiae A. S. S. S. L. A. R. Y. Genes Dev. 2002; 16: PubMed Scopus Google Scholar). to both are and have not as of the for a and not a consensus FeRE within region and may induced as an of the has one consensus FeRE within region and for a of the of and function are of that the use of for the an the under the of promoter and the of the used to the expression of FIT3 in the a or the with the and the The expression of FIT3 that from the that of the is that the include genes that have induced through of the and the to iron to is present in the but that response is in the the In Analysis of FET3 Aft1p and Aft2p that the regions of each are able to bind to the FET3 FeRE in vitro J.C. Jaron S. Ray E. Brown P.O. Winge D.R. Proc. Natl. Acad. Sci. U. S. A. 2001; 98: 14322-14327Crossref PubMed Scopus (129) Google Scholar). both the and the expression of of the same genes, used to both factors through the same FeRE in The first contains of the FET3 has to the gene gene in the of the FeRE to the to the is to a FeRE (14Yamaguchi-iwai Y. Stearman R. Dancis A. Klausner D. EMBO J. 1996; 15: 3377-3384Crossref PubMed Scopus (292) Google Scholar). The of the same FET3 FeRE within a that an upstream The contains a within the FeRE (14Yamaguchi-iwai Y. Stearman R. Dancis A. Klausner D. EMBO J. 1996; 15: 3377-3384Crossref PubMed Scopus (292) Google Scholar). and and their the either or used to the expression of the genes. Both the and induced the expression of in and but not the genes a FeRE In both the induced expression of the genes the by the The is a activator of the FET3 J.C. Jaron S. Ray E. Brown P.O. Winge D.R. Proc. Natl. Acad. Sci. U. S. A. 2001; 98: 14322-14327Crossref PubMed Scopus (129) Google the of this with these particular may due to the of upstream of the FET3 promoter region that are in and In Analysis of FIT3 induced gene by the and is FIT3 and the that both Aft1p and Aft2p the expression of FIT3 through the same a of the FIT3 to that the region of the induced expression of the of There are FeRE within the of FIT3 that each from the consensus FeRE by one of an FeRE have the same for both and a gene that in of these FeRE The FeRE to the and the that either or of the FeRE both the and induced expression of the Both of these FeRE from the consensus FeRE in their with this being for by Aft1p and In with the the is a stronger activator the of the expression of the of the expression of the and genes is with the and expression through the same FeRE. In Analysis of MRS4 have shown that MRS4 is induced by the J.C. Jaron S. Ray E. Brown P.O. Winge D.R. Proc. Natl. Acad. Sci. U. S. A. 2001; 98: 14322-14327Crossref PubMed Scopus (129) Google Scholar). the region of MRS4 contains that each from the consensus FeRE by the and the expression of MRS4 through these FeRE a of of the MRS4 upstream region These the either or The of at in the with one site not in that with the the is a stronger activator of the expression of the that Aft1p and Aft2p induce expression through one of these each within the the and upstream of the to a FeRE The with the in the site the of the site in the of and expression Aft1p and Aft2p the expression of MRS4 through a variant and Aft2p regulate the expression of MRS4 through a variant FeRE. contains of the upstream region of MRS4 to the or used to of from the that with and with the contains and in each to a FeRE. in to The for each is the gene, and the is the The expression from the MRS4 FeRE by Aft2p due to Aft2p a for that particular site may other in the MRS4 promoter the of Aft1p and Aft2p to transcription via this FeRE in a different promoter the the site of that is within a promoter that is to the the either or The expression of the gene in the the in the same the of in the the same of expression not The of transcription by Aft2p from the MRS4 FeRE is therefore not other within the MRS4 promoter of an used to the to the FeRE within the region of the genes by the a to within of the the genes within and of The that is with the FeRE that the is with in vivo of the of We genes within and that the consensus FeRE the in either within of their the genes that at one of this FeRE are to both to this FeRE being present in of the genes of the of a one FeRE within the same this that of the FeRE by We therefore for genes that at one of the in either within their the genes in and genes this FeRE of genes with within the of the genes a of genes that an FeRE in that group of genes that are induced in either of the or S. cerevisiae contains paralogous iron-responsive transcription factors, Aft1p and Aft2p J.C. Jaron S. Ray E. Brown P.O. Winge D.R. Proc. Natl. Acad. Sci. U. S. A. 2001; 98: 14322-14327Crossref PubMed Scopus (129) Google Scholar). In the present the and used to the global gene expression that is by each We show for the first time that the and in distinct global transcriptional they are within the same The genes that are induced by Aft1p and Aft2p a of different There are genes that encode for of iron that are induced to an by both Aft1p and However, a group of the activated iron-regulated genes are more induced by expression of FET3 is by the with by the There are genes that a consensus FeRE that are induced by either Aft1p or Aft2p but not In the of the genes and the function of these genes is with Aft1p these genes. In the of the genes and is not the FeRE within their promoter regions are Aft2p these genes. There are also genes that not a consensus or an within their upstream that are induced in that the of function The of these genes is to as the of the of Aft1p and The differential of by Aft1p and Aft2p is Yap2p is a transcription factor and differential expression by Aft1p and Aft2p may in for the different and global gene The unique transcriptional therefore from the gene by Aft1p and Aft2p and the of the expression of genes that are not in the iron regulon. In are with other that have genes that are regulated in response to iron. These include individual genes that are activated by the genes within the iron regulon that are activated in response to and genes that are activated in a that a a that is involved in C.-W. Ferea T. Rashford J. Ardon O. Brown P.O. Botstein D. Kaplan J. Philpott C.C. J. Biol. Chem. 2000; 275: 10709-10715Abstract Full Text Full Text PDF PubMed Scopus (165) Google Scholar, 12Foury F. Talibi D. J. Biol. Chem. 2001; 276: 7762-7768Abstract Full Text Full Text PDF PubMed Scopus (161) Google Scholar, O. Ferea T. Rashford J. Tiedeman J. Brown P.O. Botstein D. Philpott C.C. J. Biol. Chem. 2001; 276: 49244-49250Abstract Full Text Full Text PDF PubMed Scopus (134) Google Scholar, Y. Stearman R. Dancis A. Klausner D. EMBO J. 1996; 15: 3377-3384Crossref PubMed Scopus (292) Google Scholar, S. Kaplan J. Proc. Natl. Acad. Sci. U. S. A. 2002; PubMed Scopus Google Scholar, J. J. Biol. Chem. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar). There between these the of the of function a of genes that are activated by the factors but are not induced in a These genes include and In this particular these in global gene expression may from the pleiotropic of in a Analysis of the promoter regions of the genes that are induced by the factors to the of an FeRE. FeRE includes the consensus FeRE with an is that regions of can and transcription factor function E. 2000; PubMed Google Scholar). is to the of this FeRE. low have shown for the first time that Aft1p and Aft2p mediate gene through the same in Both Aft1p and Aft2p the expression of a gene that is under the of a promoter that contains the consensus FeRE from In a using of within the FIT3 promoter in the of the or of a that both these FeRE from the consensus FeRE at the These are with the that a an the of and the is more to low iron conditions the C. C. C. R. E. 1997; 13: PubMed Scopus Google Scholar). a the Aft1p able to with Aft2p for binding to particular and Aft2p from the iron regulon. In to transcriptional via a consensus have also shown that both Aft1p and Aft2p regulate MRS4 through a variant FeRE. has as an iron F. T. J. Biol. Chem. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar). MRS4 contains within upstream region that the The MRS4 site is an as of the in this site the of a gene by Aft1p and In addition, this FeRE is within a promoter transcriptional in an is with the of MRS4 by Aft2p being due to the variant FeRE and not other within the MRS4 promoter site from the consensus FeRE site as contains upstream of the is that a DNA a FeRE with in an in vitro (14Yamaguchi-iwai Y. Stearman R. Dancis A. Klausner D. EMBO J. 1996; 15: 3377-3384Crossref PubMed Scopus (292) Google Scholar). The as with the is the more potent activator of The of other FeRE that from the consensus FeRE and the of binding to different FeRE by Aft1p and Aft2p are for that in and not the of a consensus FeRE within the promoter region of a particular The from this are with both Aft1p and Aft2p gene expression through promoter elements and each being for different transcriptional profiles. the of by Aft1p and Aft2p to the using the each transcription factor to the of for the same promoter The is to Aft1p and Aft2p interact with both are present in The paralogous factors Yap1p/Yap2p and Pdr1p/Pdr3p may bind as to their promoter The are not and to has the of Aft1p or Aft1p and Aft2p can of different transcriptional that different global gene expression by of Aft1p and Aft2p hetero- and Aft1p and Aft2p not they bind to the of each The therefore to the factors for the same and each factor have the same or different for particular In addition, the of each factor the of particular Aft1p from the to the under low iron Aft2p is may a different cellular of iron that may the of the by We are in the of the cellular of Aft2p in response to iron. There are genes that are regulated by one of the is and not the iron genes, and is that other proteins are involved in the promoter selectivity of Aft1p and Aft2p at Alternatively, gene may to the of transcriptional that is by Aft1p and There is in the domains of each to both Aft1p and Aft2p can bind to the same upstream region of genes that FeRE to hetero- and homodimers binding to the same the binding of both Aft1p and Aft2p factors to in the same promoter region in a response to iron the of each by has not F. Simon J. E. 2002; PubMed Scopus Google and have Church G.M. Mol. Cell. Biol. 2000; PubMed Scopus Google using that but not is induced in response to with the not is with other that have shown that paralogous genes that have can regulated in response to different conditions O. G. Botstein D. Brown P.O. Mol. Biol. Cell. 2000; PubMed Scopus Google Scholar). may a of an or an transcriptional profile under a particular of cellular promoter by both Aft1p and Aft2p under different cellular conditions in vivo and of Aft1p and Aft2p binding to different in vitro of transcriptional in S. We the of the of by and by the We of to the for DNA at the of