Functional Analysis of the Zn2Cys6Transcription Factors Oaf1p and Pip2p

Fatty acid induction of the peroxisomal β-oxidation machinery in Saccharomyces cerevisiaeinvolves transcriptional control of genes regulated by the oleate response element (ORE). Glucose as the preferred carbon source antagonizes this effect. Induction is dependent on the Zn2Cys6 family members Oaf1p and Pip2p, which bind to this element as a heterodimer. We show here by ectopically expressing both components and LexA fusion derivatives that this transcription factor complex is only active in the presence of oleate. In contrast to Pip2p, Oaf1p is responsive to oleate activation in the absence of the other component of the heterodimer. Therefore, it is the exclusive receptor of the oleate signal. Pip2p is active also under noninducing conditions but is effectively inhibited when complexed with Oaf1p in the absence of inducer. It contributes to the trans-activation properties of the Oaf1p-Pip2p heterodimer and is required for efficient binding of Oaf1p to OREs in vivo. Repression of ORE-dependent transcription by glucose occurs via both Oaf1p and Pip2p. By dissecting functional domains of both proteins, we identified a region required for regulated activity of the C-terminal activation domain. These findings allow us to postulate a model for carbon source-regulated transcription of peroxisomal protein genes. Fatty acid induction of the peroxisomal β-oxidation machinery in Saccharomyces cerevisiaeinvolves transcriptional control of genes regulated by the oleate response element (ORE). Glucose as the preferred carbon source antagonizes this effect. Induction is dependent on the Zn2Cys6 family members Oaf1p and Pip2p, which bind to this element as a heterodimer. We show here by ectopically expressing both components and LexA fusion derivatives that this transcription factor complex is only active in the presence of oleate. In contrast to Pip2p, Oaf1p is responsive to oleate activation in the absence of the other component of the heterodimer. Therefore, it is the exclusive receptor of the oleate signal. Pip2p is active also under noninducing conditions but is effectively inhibited when complexed with Oaf1p in the absence of inducer. It contributes to the trans-activation properties of the Oaf1p-Pip2p heterodimer and is required for efficient binding of Oaf1p to OREs in vivo. Repression of ORE-dependent transcription by glucose occurs via both Oaf1p and Pip2p. By dissecting functional domains of both proteins, we identified a region required for regulated activity of the C-terminal activation domain. These findings allow us to postulate a model for carbon source-regulated transcription of peroxisomal protein genes. In the yeast Saccharomyces cerevisiae fatty acids such as oleate cause a massive proliferation of the peroxisomal compartment accompanied by the induction of β-oxidation (1Veenhuis M. Mateblowski M. Kunau W.-H. Harder W. Yeast. 1987; 3: 77-84Crossref PubMed Scopus (234) Google Scholar). Glucose represses these effects apparently because it is utilized preferably to alternative carbon sources such as fatty acids (2Simon M. Adam G. Rapatz W. Spevak W. Ruis H. Mol. Cell. Biol. 1991; 11: 699-704Crossref PubMed Scopus (130) Google Scholar, 3Stanway C.A. Gibbs J.M. Berardi E. Curr. Genet. 1995; 27: 404-408Crossref PubMed Scopus (17) Google Scholar, 4Gancedo J.M. Microbiol. Mol. Biol. Rev. 1998; 62: 1092-2172Crossref Google Scholar). Glucose repression predominantly affects gene expression and is often mediated by the action of Mig1p (5Ronne H. Trends Genet. 1995; 11: 12-17Abstract Full Text PDF PubMed Scopus (382) Google Scholar, 6Carlson M. Curr. Opin. Genet. Dev. 1998; 8: 560-564Crossref PubMed Scopus (72) Google Scholar, 7Johnston M. Trends Genet. 1999; 15: 29-33Abstract Full Text Full Text PDF PubMed Scopus (321) Google Scholar). However, alternative mechanisms must exist for fatty acid-inducible genes since they are not regulated via Mig1p (3Stanway C.A. Gibbs J.M. Berardi E. Curr. Genet. 1995; 27: 404-408Crossref PubMed Scopus (17) Google Scholar, 8Einerhand A.W.C. Kos W. Smart W.C. Kal A.J. Tabak H.F. Cooper T.G. Mol. Cell. Biol. 1995; 15: 3405-3414Crossref PubMed Scopus (33) Google Scholar). Fatty acid-mediated induction is based on a dramatic increase in transcription of several genes encoding peroxisomal functions due to the presence of an oleate response element (ORE) 1The abbreviations used are: ORE, oleate response element; AD, trans-activation domain; DMS, dimethyl sulfate; PCR, polymerase chain reaction; bp, base pair; kb, kilobase pair in their promoters (9Einerhand A.W.C. Kos W.T. Distel B. Tabak H.F. Eur. J. Biochem. 1993; 214: 323-331Crossref PubMed Scopus (71) Google Scholar,10Filipits M. Simon M.M. Rapatz W. Hamilton B. Ruis H. Gene (Amst.). 1993; 132: 49-55Crossref PubMed Scopus (69) Google Scholar). This upstream activating sequence is minimally defined by an inverted repeat of CGG triplets separated by a 15–18-nucleotide spacer. It constitutes the binding target for the transcription factors Oaf1p and Pip2p (11Luo Y. Karpichev I.V. Kohanski R. Small G.M. J. Biol. Chem. 1996; 271: 12068-12075Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar, 12Rottensteiner H. Kal A.J. Filipits M. Binder M. Hamilton B. Tabak H.F. Ruis H. EMBO J. 1996; 15: 2924-2934Crossref PubMed Scopus (96) Google Scholar). These two proteins are quite similar with an overall identity of 40% and belong to the Zn2Cys6 protein family of fungal transcription factors. Usually, members of this family require homodimerization to be able to bind their cognate sites. Oaf1p and Pip2p, however, predominantly bind to OREs as a heterodimeric complex (13Karpichev I.V. Luo Y. Marians R.C. Small G.M. Mol. Cell. Biol. 1997; 17: 69-80Crossref PubMed Google Scholar, 14Rottensteiner H. Kal A.J. Hamilton B. Ruis H. Tabak H.F. Eur. J. Biochem. 1997; 247: 776-783Crossref PubMed Scopus (100) Google Scholar). Transcription of PIP2 is itself up-regulated by oleate via an ORE in its promoter and thus requires Pip2p and Oaf1p, whereas expression of OAF1 is independent of these factors and comparable in glucose, ethanol, and oleate medium (14Rottensteiner H. Kal A.J. Hamilton B. Ruis H. Tabak H.F. Eur. J. Biochem. 1997; 247: 776-783Crossref PubMed Scopus (100) Google Scholar). Functional domains other than the N-terminal Zn2Cys6 DNA-binding motifs have not yet been identified in Oaf1p or Pip2p. The domain structures of Oaf1p and Pip2p may deviate from the functional organization of a prototypic Zn2Cys6 protein homodimer (15Schjerling P. Holmberg S. Nucleic Acids Res. 1996; 24: 4599-4607Crossref PubMed Scopus (226) Google Scholar) as they have to allow the formation of a heterodimer in order to function properly. Moreover, the mechanisms required to convert Zn2Cys6 proteins from an inactive to an active state are apparently not conserved. Activation of Gal4p, for instance, depends on its interaction with Gal80p- and Gal3p-binding galactose (16Yano K. Fukasawa T. Proc. Natl. Acad. Sci. U. S. A. 1997; 94: 1721-1726Crossref PubMed Scopus (90) Google Scholar, 17Blank T.E. Woods M.P. Lebo C.M. Xin P. Hopper J.E. Mol. Cell. Biol. 1997; 17: 2566-2575Crossref PubMed Scopus (62) Google Scholar), whereas phosphorylation via the Snf1p (Cat1p) protein kinase suffices to activate Cat8p and Sip4p (18Randez-Gil F. Bojunga N. Proft M. Entian K.-D. Mol. Cell. Biol. 1997; 17: 2502-2510Crossref PubMed Scopus (106) Google Scholar, 19Rahner A. Scholer A. Martens E. Gollwitzer B. Schüller H.J. Nucleic Acids Res. 1996; 24: 2331-2337Crossref PubMed Scopus (72) Google Scholar, 20Lesage P. Yang X. Carlson M. Mol. Cell. Biol. 1996; 16: 1921-1928Crossref PubMed Scopus (105) Google Scholar). These recent findings challenge the idea of a common principle in Zn2Cys6 protein regulation and highlight the requirement for a detailed study on the inducer-mediated activation of the Oaf1p-Pip2p transcription factor. This report is concerned with the individual roles of Pip2p and Oaf1p in activation of transcription by fatty acids and its repression by glucose and addresses the domain structure of Oaf1p and Pip2p. The results are a model for carbon transcription of genes. and used are in and in cerevisiae or PubMed Google M. Adam G. Rapatz W. Spevak W. Ruis H. Mol. Cell. Biol. 1991; 11: 699-704Crossref PubMed Scopus (130) Google M. Simon M.M. Rapatz W. Hamilton B. Ruis H. Gene (Amst.). 1993; 132: 49-55Crossref PubMed Scopus (69) Google H. Kal A.J. Filipits M. Binder M. Hamilton B. Tabak H.F. Ruis H. EMBO J. 1996; 15: 2924-2934Crossref PubMed Scopus (96) Google H. Kal A.J. Hamilton B. Ruis H. Tabak H.F. Eur. J. Biochem. 1997; 247: 776-783Crossref PubMed Scopus (100) Google H. Kal A.J. Filipits M. Binder M. Hamilton B. Tabak H.F. Ruis H. EMBO J. 1996; 15: 2924-2934Crossref PubMed Scopus (96) Google H. Kal A.J. Hamilton B. Ruis H. Tabak H.F. Eur. J. Biochem. 1997; 247: 776-783Crossref PubMed Scopus (100) Google H. Kal A.J. Hamilton B. Ruis H. Tabak H.F. Eur. J. Biochem. 1997; 247: 776-783Crossref PubMed Scopus (100) Google from from from from from from H. Kal A.J. Hamilton B. Ruis H. Tabak H.F. Eur. J. Biochem. 1997; 247: 776-783Crossref PubMed Scopus (100) Google from H. Kal A.J. Hamilton B. Ruis H. Tabak H.F. Eur. J. Biochem. 1997; 247: 776-783Crossref PubMed Scopus (100) Google from H. Kal A.J. Hamilton B. Ruis H. Tabak H.F. Eur. J. Biochem. 1997; 247: 776-783Crossref PubMed Scopus (100) Google from from from from from from from from from in a or A. Gene (Amst.). PubMed Scopus Google A. Gene (Amst.). PubMed Scopus Google H. Kal A.J. Hamilton B. Ruis H. Tabak H.F. Eur. J. Biochem. 1997; 247: 776-783Crossref PubMed Scopus (100) Google of the H. Kal A.J. Hamilton B. Ruis H. Tabak H.F. Eur. J. Biochem. 1997; 247: 776-783Crossref PubMed Scopus (100) Google under the H. Kal A.J. Filipits M. Binder M. Hamilton B. Tabak H.F. Ruis H. EMBO J. 1996; 15: 2924-2934Crossref PubMed Scopus (96) Google of the under its H. Kal A.J. Filipits M. Binder M. Hamilton B. Tabak H.F. Ruis H. EMBO J. 1996; 15: 2924-2934Crossref PubMed Scopus (96) Google under its H. Kal A.J. Hamilton B. Ruis H. Tabak H.F. Eur. J. Biochem. 1997; 247: 776-783Crossref PubMed Scopus (100) Google to H. Kal A.J. Filipits M. Binder M. Hamilton B. Tabak H.F. Ruis H. EMBO J. 1996; 15: 2924-2934Crossref PubMed Scopus (96) Google to to to to to to to to to to to to to to to to to to to to to to to of of in a in medium yeast glucose to of in medium with glucose from or in medium yeast glucose, acids as from and for The to medium glucose or acid to with and the an of in of Oaf1p and Pip2p for their to on that and for formation as H. Kal A.J. Filipits M. Binder M. Hamilton B. Tabak H.F. Ruis H. EMBO J. 1996; 15: 2924-2934Crossref PubMed Scopus (96) Google Scholar). the of the promoter by with from the pair and The used to the promoter in H. Kal A.J. Filipits M. Binder M. Hamilton B. Tabak H.F. Ruis H. EMBO J. 1996; 15: 2924-2934Crossref PubMed Scopus (96) Google Scholar). the the fusion the in A. Gene (Amst.). PubMed Scopus Google Scholar) to by the of with that from (14Rottensteiner H. Kal A.J. Hamilton B. Ruis H. Tabak H.F. Eur. J. Biochem. 1997; 247: 776-783Crossref PubMed Scopus (100) Google Scholar) by an of the with the (14Rottensteiner H. Kal A.J. Hamilton B. Ruis H. Tabak H.F. Eur. J. Biochem. 1997; 247: 776-783Crossref PubMed Scopus (100) Google Scholar). and and the of the M. Simon M.M. Rapatz W. Hamilton B. Ruis H. Gene (Amst.). 1993; 132: 49-55Crossref PubMed Scopus (69) Google Scholar). of the ORE with to fusion by as M. Simon M.M. Rapatz W. Hamilton B. Ruis H. Gene (Amst.). 1993; 132: 49-55Crossref PubMed Scopus (69) Google Scholar). H. Kal A.J. Filipits M. Binder M. Hamilton B. Tabak H.F. Ruis H. EMBO J. 1996; 15: 2924-2934Crossref PubMed Scopus (96) Google Scholar). of the base from the of a with the pair LexA and as a The with and an H. Kal A.J. Filipits M. Binder M. Hamilton B. Tabak H.F. Ruis H. EMBO J. 1996; 15: 2924-2934Crossref PubMed Scopus (96) Google Scholar). of the and the of by a with the and this used in with the the of to the of the gene to its of the and a to the of The used to the region of PIP2 that to its as for of the of and the region that to its as the and the of the two a of with and of base from the of a with the pair and as a The to a that the of the two with of a with the pair and as a The with and the as for a with the pair and as a The with and the of a with the pair and H. Kal A.J. Filipits M. Binder M. Hamilton B. Tabak H.F. Ruis H. EMBO J. 1996; 15: 2924-2934Crossref PubMed Scopus (96) Google Scholar) as a The with and and the of a with the pair and as a The with and the of the and the been by a of by with by a and a of the a with the pair and as a The with and and the the OAF1 of a with the pair and from The OAF1 with and the a with the pair and (14Rottensteiner H. Kal A.J. Hamilton B. Ruis H. Tabak H.F. Eur. J. Biochem. 1997; 247: 776-783Crossref PubMed Scopus (100) Google Scholar) as a The with and and the of a with the pair and from as a The with and a with of and by with polymerase to The of the two and of a with the pair and as a The with and the of with and the of the and of with and and with to The and of a from with the pair and The with and and an a with the pair and from as a The with and and in the of a with the pair and from as a The with and and a the the and H. Kal A.J. Filipits M. Binder M. Hamilton B. Tabak H.F. Ruis H. EMBO J. 1996; 15: 2924-2934Crossref PubMed Scopus (96) Google Scholar). a from an a (14Rottensteiner H. Kal A.J. Hamilton B. Ruis H. Tabak H.F. Eur. J. Biochem. 1997; 247: 776-783Crossref PubMed Scopus (100) Google Scholar) as a and the pair and The an A. Gene (Amst.). PubMed Scopus Google Scholar). Pip2p or by of and the of the the gene by of the of the or by on the In dimethyl a as W. E. F. G. Hamilton B. Ruis H. Schüller Dev. 1998; PubMed Scopus Google Scholar). In and in medium glucose to an of to and for and in of the for The by of and used as a for with the for of the and to the separated on an and a in a and a of separated by PubMed Scopus Google Scholar), and to of proteins from J. of J. The and The used or with from The proteins to the The to acid J. T. Scholar), yeast H. Y. K. J. PubMed Google Scholar), acid F. S. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar), of protein M.M. Biochem. PubMed Scopus Google Scholar), and for activity in Scholar). are the of results in in PIP2 or OAF1 are to genes in the presence of oleate (11Luo Y. Karpichev I.V. Kohanski R. Small G.M. J. Biol. Chem. 1996; 271: 12068-12075Abstract Full Text Full Text PDF PubMed Scopus (59) Google H. Kal A.J. Filipits M. Binder M. Hamilton B. Tabak H.F. Ruis H. EMBO J. 1996; 15: 2924-2934Crossref PubMed Scopus (96) Google Scholar). of of the Pip2p, however, itself by oleate via an ORE in its promoter (14Rottensteiner H. Kal A.J. Hamilton B. Ruis H. Tabak H.F. Eur. J. Biochem. 1997; 247: 776-783Crossref PubMed Scopus (100) Google Scholar). It the requirement for oleate by the induction machinery be by PIP2 in the absence of oleate. that a of PIP2 or under the control of the promoter and a The promoter because of its activity in the absence of expression of in glucose medium but in and oleate In the absence of however, expression of a not oleate to activate the Oaf1p-Pip2p heterodimer when Pip2p of the two proteins or both of the signal. It a component of the heterodimer when from the promoter suffices to activate a gene in an of in a comparable in and oleate that the gene activity for a in the presence of oleate due to transcription of in also similar in the presence of and oleate However, Pip2p only expression of the increase This may that the trans-activation of Pip2p also in the presence of oleate. The may have been by Pip2p to bind to the ORE in the absence of Oaf1p 14Rottensteiner H. Kal A.J. Hamilton B. Ruis H. Tabak H.F. Eur. J. Biochem. 1997; 247: 776-783Crossref PubMed Scopus (100) Google and not that not on binding to OREs required to allow a of the transcriptional of Oaf1p and Pip2p. this Pip2p and Oaf1p to LexA and for their to activate proteins functional in their fusion to LexA as they the oleate in the a of under the control of the the fusion to comparable in glucose, ethanol, and oleate In able to transcriptional activation only in the presence of oleate that this expression not dependent on with Pip2p or Oaf1p, the fusion protein also in in or both genes. the activation in such not deviate from that in the a transcriptional in the presence of or but induction not in the or of the This is in contrast to a by H. Kal A.J. Filipits M. Binder M. Hamilton B. Tabak H.F. Ruis H. EMBO J. 1996; 15: 2924-2934Crossref PubMed Scopus (96) Google Scholar). However, the also and that are not by oleate. both proteins only Oaf1p is able to the oleate and Oaf1p C-terminal with expressing LexA with of Pip2p or Oaf1p as in glucose or oleate and for gene with source regulation of transcriptional activation of Pip2p and Oaf1p requires an domain. The LexA with of Pip2p or Oaf1p in for activity in glucose and oleate with induction is by the presence of glucose, expression is (14Rottensteiner H. Kal A.J. Hamilton B. Ruis H. Tabak H.F. Eur. J. Biochem. 1997; 247: 776-783Crossref PubMed Scopus (100) Google Scholar). However, it that the activity of the Oaf1p-Pip2p complex is by It the of the LexA of Oaf1p and Pip2p be by glucose in the presence of oleate. in glucose effectively the transcriptional activity of Pip2p in the presence of oleate both in and activation of Oaf1p also when glucose similar results when the Oaf1p fusion in an it that Oaf1p is only able to to oleate in the absence of glucose and that both factors are of glucose represses the of Pip2p and in a Oaf1p the requirement for Pip2p in ORE the of the Oaf1p homodimer to to oleate induction in a ORE binding activity of an Oaf1p for this been in (14Rottensteiner H. Kal A.J. Hamilton B. Ruis H. Tabak H.F. Eur. J. Biochem. 1997; 247: 776-783Crossref PubMed Scopus (100) Google Scholar). The binding of ORE in by from as a for since it only that are not by proteins W. E. F. G. Hamilton B. Ruis H. Schüller Dev. 1998; PubMed Scopus Google Scholar). a of promoter the to the ORE and from of with of to of the CGG triplets of the ORE that these in complex these only from in the absence of Pip2p, Oaf1p, or both factors that a in binding of an Oaf1p homodimer is for the in a The results that their Oaf1p and Pip2p not functions in the regulation of fatty acid It to of both transcription factors to of the two LexA with of Pip2p and Oaf1p for their transcriptional on carbon In comparable expression of fusion proteins by in of Pip2p that the to gene activity that the C-terminal region of Pip2p trans-activation of these the oleate induction in with and which the the LexA from the PIP2 such be The of the C-terminal region for trans-activation by C-terminal acids of and C-terminal acids of which expression of the gene on and oleate defined an trans-activation domain of Pip2p to its acid it Oaf1p a in and also in activating transcription of the these two as as expressing the from the promoter not an on oleate and trans-activation properties that Oaf1p also an its C-terminal acid The of both Oaf1p and Pip2p to glucose as is in by the of and in the presence of oleate and only an repression by glucose it in a control LexA to the a similar effect. a on with glucose glucose repression in the presence of oleate in the of the a glucose repression on Pip2p and Oaf1p via their to for other in glucose of Pip2p and Oaf1p are of glucose in a of the N-terminal acids of Pip2p the binding domain in of the oleate induction of a but by glucose comparable to the the N-terminal the activity with Pip2p, but a repression of activity in the presence of glucose This that the region acids and in regulation but not in glucose By a acids from the an inactive fusion protein the C-terminal a fusion of LexA with acid of Pip2p it that this region not an independent It to in the function of the C-terminal in the of the protein and domain. that acids an increase in activity when with Pip2p but also to glucose repression Pip2p a domain acid a activity comparable to Pip2p, this domain is acids and These that the domain may the target for glucose repression in Pip2p. of and comparable on and oleate but than that with Oaf1p on oleate an activation that of the Pip2p which are also not responsive to oleate. activation when and that as as domains have to be N-terminal to acid The of gene activity or that an domain is acid and that the to the of In Pip2p, a N-terminal domain activity and in Therefore, to This fusion protein the binding domain of Oaf1p and not able to the oleate of an However, able to activate its activity regulated by oleate. an domain be to the region and and a region for to oleate acid and activity mediated by with Oaf1p under conditions a region to be by the N-terminal acid of heterodimer of two fungal transcription Oaf1p and Pip2p, been to be for ORE-dependent oleate induction of transcription in the yeast S. cerevisiae (13Karpichev I.V. Luo Y. Marians R.C. Small G.M. Mol. Cell. Biol. 1997; 17: 69-80Crossref PubMed Google Scholar, 14Rottensteiner H. Kal A.J. Hamilton B. Ruis H. Tabak H.F. Eur. J. Biochem. 1997; 247: 776-783Crossref PubMed Scopus (100) Google Scholar). here to the that Oaf1p is the receptor for the oleate signal. This is by the Oaf1p in the absence of Pip2p a oleate induction of a fusion protein mediated induction of a gene in an in of the oleate It is that oleate activation of Pip2p by an interaction with the LexA in the fusion with Pip2p. results show that oleate induction occurs via the Oaf1p component of the heterodimer. the other have similar on oleate (13Karpichev I.V. Luo Y. Marians R.C. Small G.M. Mol. Cell. Biol. 1997; 17: 69-80Crossref PubMed Google Scholar, 14Rottensteiner H. Kal A.J. Hamilton B. Ruis H. Tabak H.F. Eur. J. Biochem. 1997; 247: 776-783Crossref PubMed Scopus (100) Google Scholar). This to the of Pip2p. in in this study that binding is only efficient when an Oaf1p-Pip2p heterodimer be However, it is that Pip2p is than a protein since as a LexA fusion protein it transcriptional activity comparable to that of the Oaf1p fusion This that the activation of the heterodimer by Pip2p contributes to its trans-activation of Pip2p on not to ORE-dependent activation of transcription its comparable on and oleate in a It that in a heterodimeric Pip2p activity is regulated by oleate in an We postulate that Pip2p activity is effectively inhibited by its interaction with Oaf1p oleate is for Pip2p complexed to Oaf1p also in the absence of oleate (13Karpichev I.V. Luo Y. Marians R.C. Small G.M. Mol. Cell. Biol. 1997; 17: 69-80Crossref PubMed Google Scholar, A. H. Binder M. Ruis H. Hamilton B. Mol. Microbiol. 1997; PubMed Scopus Google Scholar). Pip2p in to Oaf1p because of not bind to OREs and also not activate In the fusion protein not require ORE binding and activity also in the absence of from the be in to Oaf1p, it is that Oaf1p not able to transcription under these conditions it with The detailed mechanisms of carbon source regulation of activity of the heterodimer are not yet here have that Pip2p and Oaf1p are similar not only in their acid sequence but also in their domain structure identified in both proteins to the similar to identified in other members of the Zn2Cys6 protein family (15Schjerling P. Holmberg S. Nucleic Acids Res. 1996; 24: 4599-4607Crossref PubMed Scopus (226) Google Scholar). domains have been to both proteins and not in carbon source signal. properties have been to the region of other Zn2Cys6 protein family members Mol. Cell. Biol. PubMed Scopus Google Scholar, G. EMBO J. 1993; PubMed Scopus Google Scholar, 1996; Google Scholar, Mol. Cell. Biol. 1996; 16: PubMed Scopus Google Scholar, E. A. E. A. Mol. Genet. 1997; PubMed Scopus Google Scholar, A. A. J. Mol. Genet. 1997; PubMed Scopus Google Scholar, Y. J. Biol. Chem. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar). this to the of a domain or region (15Schjerling P. Holmberg S. Nucleic Acids Res. 1996; 24: 4599-4607Crossref PubMed Scopus (226) Google Scholar, Mol. Cell. Biol. PubMed Scopus Google Scholar, Gene (Amst.). 1997; PubMed Scopus Google Scholar), the of this region in transcriptional activity It may be required to the via or in the absence of the transcription factor in a and domain required for regulated activity of both Pip2p and In Pip2p, the element to be of this domain. In Oaf1p, this region may also since activation by oleate been here to on a region acid and the presence of the domain in active fusion proteins than it may be that it also the of the two It is that of function in the Zn2Cys6 proteins and to be in a region E. A. E. A. Mol. Genet. 1997; PubMed Scopus Google Scholar, A. A. J. Mol. Genet. 1997; PubMed Scopus Google Scholar). have to the domain is in carbon source regulation or as a for of other domains in Oaf1p or Pip2p. In the in this study allow us to a model of the of Oaf1p and Pip2p in fatty transcription of genes encoding peroxisomal proteins but carbon sources such as ethanol, Oaf1p is The activity of Pip2p is in the heterodimeric complex with Oaf1p, and OREs genes encoding peroxisomal proteins are to a under such it is that of peroxisomal functions is by promoter other than the ORE the element (2Simon M. Adam G. Rapatz W. Spevak W. Ruis H. Mol. Cell. Biol. 1991; 11: 699-704Crossref PubMed Scopus (130) Google Scholar). induction of proliferation by fatty Oaf1p which is also to an of the Pip2p This induction of Pip2p and the formation of of the heterodimeric transcription which to The of oleate be by mechanisms to glucose repression of genes encoding peroxisomal functions A.W.C. Kos W. Smart W.C. Kal A.J. Tabak H.F. Cooper T.G. Mol. Cell. Biol. 1995; 15: 3405-3414Crossref PubMed Scopus (33) Google Scholar, Mol. Cell. Biol. PubMed Google Scholar, Mol. Cell. Biol. 1997; 17: PubMed Scopus Google Scholar). identified in the of this study a of the of Pip2p and of the transcription factor a of ORE-dependent transcription and a glucose this carbon source is We and for for for and for for the and J. Kal for the We also and Schüller for