ࡱ > o q q @ K bjbj $ p$ ' v v v v v v v V V V 8 J f . H ( p p p r l 8 e e e e e e e $ eh R j @e v @e v v p p 4 !f ` K K K v p v p ` K e K K $ t v v P* p 2f_ V ( : f- 3 f H f B( ?k r ?k t P* v v v v P* J ?k v * L 6 K < , h q @e @e $ X $ Supporting Information Protocol S1
Promoter Models
Biological Justification of Wildtype Model Structure
The yeast RP gene system employs the Forkhead (FH)type TF Fhl1, which belongs to a family of transcriptional regulators that have an evolutionarily conserved DNA-binding motif and variable activation / repression domains ADDIN EN.CITE Wijchers200614714717Wijchers, PjecBurbach, J. P. H.Smidt, M. P.Univ Utrecht, Med Ctr, Dept Pharmacol & Anat, Rudolf Magnus Inst Neurosci, NL-3584 CG Utrecht, Netherlands.
Wijchers, PJEC, Univ London Imperial Coll Sci & Technol, MRC Clin Sci Ctr, Gene Control Mechanisms & Dis Grp, Hammersmith Campus,Du Cane Rd, London W12 0NN, England.
patrick.wijchers@csc.mrc.ac.ukIn control of biology: of mice, men and FoxesBiochemical JournalBiochem. J.Biochemical JournalBiochem. J.Biochemical JournalBiochem. J.233-246397cell cycledevelopmentforkheadFoximmunoregulationtranscriptionfactorFORKHEAD TRANSCRIPTION FACTORPROTEIN-KINASE-BDNA-BINDING DOMAINEPITHELIAL TERMINAL DIFFERENTIATIONHEPATOCYTE NUCLEAR FACTOR-3SMADINTERACTION MOTIFWINGED HELIX PROTEINSREGULATORY T-CELLSFACTORAFX FOXO4GENE-EXPRESSION2006Jul0264-6021ISI:000239129800001Review<Go to ISI>://000239129800001 [1]. Many of these TFs share the following features: (i) they can switch between a repressive and an activating form depending on interaction partners and / or protein modification state ADDIN EN.CITE Cherel1995858517Cherel, I.Thuriaux, P.Cea saclay,serv biochim & genet molec,f-91191 gif sur yvette,france.YeastYeastYeastYeastYeastYeast261-270113YEASTRIBOSOMAL RNACHROMATINTRANSCRIPTIONAL ACTIVATORSSHUTTLE VECTORSDNAFAMILYSUPPRESSORMOTIF1995Mar0749-503XISI:A1995QL30700007Article<Go to ISI>://A1995QL30700007 Wittenberg2005343417Wittenberg, C.Reed, S. I.Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA.
Reed, SI, Scripps Res Inst, Dept Mol Biol, MB-7,10550 N Torrey Pines Rd, La Jolla, CA 92037 USA.
sreed@scripps.eduCell cycle-dependent transcription in yeast: promoters, transcription factors, and transcriptomesOncogeneOncogeneOncogeneOncogeneOncogeneOncogene2746-27552417transcriptioncell cyclecyclin-dependent protein kinaseSTART-SPECIFIC TRANSCRIPTIONSACCHAROMYCES-CEREVISIAEBUDDING YEASTG1 CYCLINSPOSITIVE FEEDBACKGENE-EXPRESSIONPROTEIN-KINASES-PHASEREGULATORY NETWORKSCLN3-CDC28 KINASE2005Apr0950-9232ISI:000228465800001Review<Go to ISI>://000228465800001 [2,3]; (ii) they affect chromatin structure by directly interacting with nucleosomes and / or by dynamically recruiting chromatin remodeling activities ADDIN EN.CITE Ho2002131317Ho, Y.Gruhler, A.Heilbut, A.Bader, G. D.Moore, L.Adams, S. L.Millar, A.Taylor, P.Bennett, K.Boutilier, K.Yang, L. Y.Wolting, C.Donaldson, I.Schandorff, S.Shewnarane, J.Vo, M.Taggart, J.Goudreault, M.Muskat, B.Alfarano, C.Dewar, D.Lin, Z.Michalickova, K.Willems, A. R.Sassi, H.Nielsen, P. A.Rasmussen, K. J.Andersen, J. R.Johansen, L. E.Hansen, L. H.Jespersen, H.Podtelejnikov, A.Nielsen, E.Crawford, J.Poulsen, V.Sorensen, B. D.Matthiesen, J.Hendrickson, R. C.Gleeson, F.Pawson, T.Moran, M. F.Durocher, D.Mann, M.Hogue, C. W. V.Figeys, D.Tyers, M.NatureNatureNatureNatureNatureNature180-1834156868yeastcheckpointdegradationpathwaysligasedomainrepair2002Jan 10ISI:000173159300044<Go to ISI>://000173159300044Wijchers200614714717Wijchers, PjecBurbach, J. P. H.Smidt, M. P.Univ Utrecht, Med Ctr, Dept Pharmacol & Anat, Rudolf Magnus Inst Neurosci, NL-3584 CG Utrecht, Netherlands.
Wijchers, PJEC, Univ London Imperial Coll Sci & Technol, MRC Clin Sci Ctr, Gene Control Mechanisms & Dis Grp, Hammersmith Campus,Du Cane Rd, London W12 0NN, England.
patrick.wijchers@csc.mrc.ac.ukIn control of biology: of mice, men and FoxesBiochemical JournalBiochem. J.Biochemical JournalBiochem. J.Biochemical JournalBiochem. J.233-246397cell cycledevelopmentforkheadFoximmunoregulationtranscriptionfactorFORKHEAD TRANSCRIPTION FACTORPROTEIN-KINASE-BDNA-BINDING DOMAINEPITHELIAL TERMINAL DIFFERENTIATIONHEPATOCYTE NUCLEAR FACTOR-3SMADINTERACTION MOTIFWINGED HELIX PROTEINSREGULATORY T-CELLSFACTORAFX FOXO4GENE-EXPRESSION2006Jul0264-6021ISI:000239129800001Review<Go to ISI>://000239129800001 [1,4]; and (iii) they are direct targets of nutrient and growthsignaling pathways, or they interact with partners that are controlled by these pathways via the Forkhead-associated (FHA) domain ADDIN EN.CITE Martin2004121217Martin, D. E.Soulard, A.Hall, M. N.Univ Basel, Biozentrum, Div Biochem, CH-4056 Basel, Switzerland.
Hall, MN, Univ Basel, Biozentrum, Div Biochem, Klingelbergstr 70, CH-4056 Basel, Switzerland.
m.hall@unibas.chTOR regulates ribosomal protein gene expression via PKA and the forkhead transcription factor FHL1CellCellCellCellCellCell969-9791197rna-polymerase-isaccharomyces-cerevisiaesignaling pathwaycell-growthfha domainmass-spectrometryhead proteinyeastrapamycinrecruitment2004Dec 29ISI:000226109700009<Go to ISI>://000226109700009Wijchers200614714717Wijchers, PjecBurbach, J. P. H.Smidt, M. P.Univ Utrecht, Med Ctr, Dept Pharmacol & Anat, Rudolf Magnus Inst Neurosci, NL-3584 CG Utrecht, Netherlands.
Wijchers, PJEC, Univ London Imperial Coll Sci & Technol, MRC Clin Sci Ctr, Gene Control Mechanisms & Dis Grp, Hammersmith Campus,Du Cane Rd, London W12 0NN, England.
patrick.wijchers@csc.mrc.ac.ukIn control of biology: of mice, men and FoxesBiochemical JournalBiochem. J.Biochemical JournalBiochem. J.Biochemical JournalBiochem. J.233-246397cell cycledevelopmentforkheadFoximmunoregulationtranscriptionfactorFORKHEAD TRANSCRIPTION FACTORPROTEIN-KINASE-BDNA-BINDING DOMAINEPITHELIAL TERMINAL DIFFERENTIATIONHEPATOCYTE NUCLEAR FACTOR-3SMADINTERACTION MOTIFWINGED HELIX PROTEINSREGULATORY T-CELLSFACTORAFX FOXO4GENE-EXPRESSION2006Jul0264-6021ISI:000239129800001Review<Go to ISI>://000239129800001 Wittenberg2005343417Wittenberg, C.Reed, S. I.Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA.
Reed, SI, Scripps Res Inst, Dept Mol Biol, MB-7,10550 N Torrey Pines Rd, La Jolla, CA 92037 USA.
sreed@scripps.eduCell cycle-dependent transcription in yeast: promoters, transcription factors, and transcriptomesOncogeneOncogeneOncogeneOncogeneOncogeneOncogene2746-27552417transcriptioncell cyclecyclin-dependent protein kinaseSTART-SPECIFIC TRANSCRIPTIONSACCHAROMYCES-CEREVISIAEBUDDING YEASTG1 CYCLINSPOSITIVE FEEDBACKGENE-EXPRESSIONPROTEIN-KINASES-PHASEREGULATORY NETWORKSCLN3-CDC28 KINASE2005Apr0950-9232ISI:000228465800001Review<Go to ISI>://000228465800001 [1,3,5]. In addition, several members of the TF class (e.g., Fkh2, Fhl1, FOXK1) require prior DNA binding by abundant general regulatory factors (GRFs) such as Rap1 or Mcm1 in yeast ADDIN EN.CITE Lieb2001676717Lieb, J. D.Liu, X. L.Botstein, D.Brown, P. O.Stanford Univ, Dept Biochem, Stanford, CA 94305 USA. Stanford Univ, Stanford Med Informat, Stanford, CA 94305 USA. Stanford Univ, Dept Genet, Stanford, CA 94305 USA.
Brown, PO, Stanford Univ, Dept Biochem, Stanford, CA 94305 USA.Promoter-specific binding of Rap1 revealed by genome-wide maps of protein-DNA associationNature GeneticsNature Genet.Nature GeneticsNature Genet.Nature GeneticsNature Genet.327-334284SACCHAROMYCES-CEREVISIAETELOMERIC HETEROCHROMATINYEAST TELOMERESSIR4 PROTEINSCOMPLEXSEQUENCESTRANSCRIPTIONINTERACTSDATABASETERMINI2001Aug1061-4036ISI:000170174800012Article<Go to ISI>://000170174800012 Morse2000777717Morse, R. H.New York State Dept Hlth, Wadsworth Ctr Labs & Res, Mol Genet Program, Albany, NY 12201 USA. SUNY Albany, Sch Publ Hlth, Albany, NY 12201 USA.
Morse, RH, New York State Dept Hlth, Wadsworth Ctr Labs & Res, Mol Genet Program, Albany, NY 12201 USA.RAP, RAP, open up! New wrinkles for RAP1 in yeastTrends in GeneticsTrends Genet.Trends in GeneticsTrends Genet.Trends in GeneticsTrends Genet.51-53162MEIOTIC RECOMBINATIONTRANSCRIPTIONCHROMATINDOMAINPROMOTERPROTEINBINDINGGENE2000Feb0168-9525ISI:000085135200002Article<Go to ISI>://000085135200002 Wittenberg2005343417Wittenberg, C.Reed, S. I.Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA.
Reed, SI, Scripps Res Inst, Dept Mol Biol, MB-7,10550 N Torrey Pines Rd, La Jolla, CA 92037 USA.
sreed@scripps.eduCell cycle-dependent transcription in yeast: promoters, transcription factors, and transcriptomesOncogeneOncogeneOncogeneOncogeneOncogeneOncogene2746-27552417transcriptioncell cyclecyclin-dependent protein kinaseSTART-SPECIFIC TRANSCRIPTIONSACCHAROMYCES-CEREVISIAEBUDDING YEASTG1 CYCLINSPOSITIVE FEEDBACKGENE-EXPRESSIONPROTEIN-KINASES-PHASEREGULATORY NETWORKSCLN3-CDC28 KINASE2005Apr0950-9232ISI:000228465800001Review<Go to ISI>://000228465800001 Boros2003545417Boros, J.Lim, F. L.Darieva, Z.Pic-Taylor, A.Harman, R.Morgan, B. A.Sharrocks, A. D.Univ Manchester, Sch Biol Sci, Manchester M13 9PT, Lancs, England. Univ Warsaw, Dept Genet, PL-02106 Warsaw, Poland. Univ Newcastle Upon Tyne, Sch Med, Sch Cell & Mol Biosci, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
Sharrocks, AD, Univ Manchester, Sch Biol Sci, 2-205 Stopford Bldg,Oxford Rd, Manchester M13 9PT, Lancs, England.Molecular determinants of the cell-cycle regulated Mcm1p-Fkh2p transcription factor complexNucleic Acids ResearchNucleic Acids Res.Nucleic Acids ResearchNucleic Acids Res.Nucleic Acids ResearchNucleic Acids Res.2279-2288319SERUM RESPONSE FACTORDNA-BINDING SPECIFICITIESTERNARY COMPLEXSACCHAROMYCES-CEREVISIAEYEASTPROTEINSDOMAINMCM1GENESELK-12003May0305-1048ISI:000182627700011Article<Go to ISI>://000182627700011 [3,6-8] and serum-response factor in humans ADDIN EN.CITE Freddie200719319317Freddie, Cecilie T.Ji, ZonglingMarais, AnettSharrocks, Andrew D.Functional interactions between the Forkhead transcription factor FOXK1 and the MADS-box protein SRFNucleic Acids ResearchNucl. Acids Res.Nucleic Acids ResearchNucleic Acids Res.Nucl. Acids Res.5203-521235152007August 1, 2007http://nar.oxfordjournals.org/cgi/content/abstract/35/15/5203 10.1093/nar/gkm528[9]. They share this feature with structurally similar promoters, such as certain ternary complex factors ADDIN EN.CITE Buchwalter2004515117Buchwalter, G.Gross, C.Wasylyk, B.INSERM, CNRS, Inst Genet & Biol Mol & Cellulaire, ULP, F-67404 Illkirch Graffenstaden, France.
Wasylyk, B, INSERM, CNRS, Inst Genet & Biol Mol & Cellulaire, ULP, 1,Rue Laurent Fries,BP 101142, F-67404 Illkirch Graffenstaden, France.
boh@igbmc.u-strasbg.frEts ternary complex transcription factorsGeneGeneGeneGeneGeneGene1-14324Elk-1Elk-3Elk-4NetErpSap-1Sap-2SRFMAP kinasephosphorylationimmediate early genesSERUM RESPONSE ELEMENTACTIVATED PROTEIN-KINASEIMMEDIATE-EARLY GENEC-FOS PROMOTERCREB-BINDING-PROTEINLOOP-HELIX PROTEINSERK MAPKINASEFACTOR ELK-1DNA-BINDINGGROWTH-FACTOR2004Jan0378-1119ISI:000188291100001Review<Go to ISI>://000188291100001 Sharrocks200222222217Sharrocks, A. D.Complexities in ETS-Domain Transcription Factor Function and Regulation: Lessons from the TCF (Ternary Complex Factor) SubfamilyBiochemical Society TransactionsBiochem. Soc. Trans.Biochemical Society TransactionsBiochem. Soc. Trans.Biochemical Society TransactionsBiochem. Soc. Trans.1-930220022002[10,11].
High-confidence experimental datasets ADDIN EN.CITE Wade20048817Wade, J. T.Hall, D. B.Struhl, K.Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
Struhl, K, Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
kevin@hms.harvard.eduThe transcription factor Ifh1 is a key regulator of yeast ribosomal protein genesNatureNatureNatureNatureNatureNature1054-10584327020FORK HEAD PROTEINSACCHAROMYCES-CEREVISIAEBINDING-SITESEXPRESSIONRAP1PROMOTERSEQUENCEASSOCIATIONRECRUITMENTACTIVATOR2004Dec0028-0836ISI:000225887000048Article<Go to ISI>://000225887000048 Schawalder20045517Schawalder, S. B.Kabani, M.Howald, I.Choudhury, U.Werner, M.Shore, D.Univ Geneva, Dept Mol Biol, CH-1211 Geneva 4, Switzerland. Univ Geneva, NCCR Program Frontiers Genet, CH-1211 Geneva, Switzerland. CEA Saclay, Serv Biochim & Genet Mol, F-91191 Gif Sur Yvette, France.
Shore, D, Univ Geneva, Dept Mol Biol, Sci 3,30 Quai Ernest Ansermet, CH-1211 Geneva 4, Switzerland.
David.Shore@molbio.unige.chGrowth-regulated recruitment of the essential yeast ribosomal protein gene activator Ifh1NatureNatureNatureNatureNatureNature1058-10614327020genome-wide locationfork head proteinsaccharomyces-cerevisiaeenvironmental-changesexpressionpathwayrap1bindingfhl12004Dec 23ISI:000225887000049<Go to ISI>://000225887000049[12,13] show that the yeast RP gene architecture is very generic: 91 out of 137 RP genes bind Fhl1, 83 bind Ifh1, and 74 genes bind both. These data likely underestimate the true extent of binding in vivo ADDIN EN.CITE Schawalder20045517Schawalder, S. B.Kabani, M.Howald, I.Choudhury, U.Werner, M.Shore, D.Univ Geneva, Dept Mol Biol, CH-1211 Geneva 4, Switzerland. Univ Geneva, NCCR Program Frontiers Genet, CH-1211 Geneva, Switzerland. CEA Saclay, Serv Biochim & Genet Mol, F-91191 Gif Sur Yvette, France.
Shore, D, Univ Geneva, Dept Mol Biol, Sci 3,30 Quai Ernest Ansermet, CH-1211 Geneva 4, Switzerland.
David.Shore@molbio.unige.chGrowth-regulated recruitment of the essential yeast ribosomal protein gene activator Ifh1NatureNatureNatureNatureNatureNature1058-10614327020genome-wide locationfork head proteinsaccharomyces-cerevisiaeenvironmental-changesexpressionpathwayrap1bindingfhl12004Dec 23ISI:000225887000049<Go to ISI>://000225887000049[13]. Only 15 RP promoters do not bind Rap1 in vivo, 9 of which are predicted targets of the alternative GRFs Reb1 and Abf1 ADDIN EN.CITE Lieb2001676717Lieb, J. D.Liu, X. L.Botstein, D.Brown, P. O.Stanford Univ, Dept Biochem, Stanford, CA 94305 USA. Stanford Univ, Stanford Med Informat, Stanford, CA 94305 USA. Stanford Univ, Dept Genet, Stanford, CA 94305 USA.
Brown, PO, Stanford Univ, Dept Biochem, Stanford, CA 94305 USA.Promoter-specific binding of Rap1 revealed by genome-wide maps of protein-DNA associationNature GeneticsNature Genet.Nature GeneticsNature Genet.Nature GeneticsNature Genet.327-334284SACCHAROMYCES-CEREVISIAETELOMERIC HETEROCHROMATINYEAST TELOMERESSIR4 PROTEINSCOMPLEXSEQUENCESTRANSCRIPTIONINTERACTSDATABASETERMINI2001Aug1061-4036ISI:000170174800012Article<Go to ISI>://000170174800012 [6]. Harbison et al. ADDIN EN.CITE 200412712717Harbison, C. T.Gordon, D. B.Lee, T. I.Rinaldi, N. J.Macisaac, K. D.Danford, T. W.Hannett, N. M.Tagne, J. B.Reynolds, D. B.Yoo, J.Jennings, E. G.Zeitlinger, J.Pokholok, D. K.Kellis, M.Rolfe, P. A.Takusagawa, K. T.Lander, E. S.Gifford, D. K.Fraenkel, E.Young, R. A.Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. Broad Inst, Cambridge, MA 02139 USA.
Young, RA, Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA.
efraenkel@wi.mit.edu young@wi.mit.eduTranscriptional regulatory code of a eukaryotic genomeNatureNatureNatureNatureNatureNature99-1044317004YEAST SACCHAROMYCES-CEREVISIAEBINDING-SITESSEQUENCESGCN4PROTEINSDATABASEMOTIFSGENES2004Sep0028-0836ISI:000223641500050Article<Go to ISI>://000223641500050 [14] observed high-confidence binding (p<5(10-3) of Fhl1 and of the alternative regulator Rgm1 to 106 and 3 RP genes, respectively. Hence, Rgm1 either acts indirectly or affects only a small subset of RP genes. The HMG protein Hmo1 and Fhl1 appear to bind to RP promoters cooperatively ADDIN EN.CITE Hall20067717Hall, D. B.Wade, J. T.Struhl, K.Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
Struhl, K, Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
kevin@hms.harvard.eduMolecular and Cellular BiologyMol. Cell. Biol.Molecular and Cellular BiologyMol. Cell. Biol.Molecular and Cellular BiologyMol. Cell. Biol.3672-3679269GROUP 1/2 HOMOLOGCHROMOSOMAL-PROTEINSBINDING-SITESBOX PROTEINYEASTRAP1TRANSCRIPTIONEXPRESSIONACTIVATORGENOME2006May0270-7306ISI:000236993300027Article<Go to ISI>://000236993300027 [15], but Fhl1 is stoichiometrically limiting (about 30fold ADDIN EN.CITE Ghaemmaghami20033317Ghaemmaghami, S.Huh, W.Bower, K.Howson, R. W.Belle, A.Dephoure, N.O'Shea, E. K.Weissman, J. S.Global analysis of protein expression in yeastNatureNatureNatureNatureNatureNature737-7414256959saccharomyces-cerevisiaemessenger-rnagene deletiongenomeidentificationhybridizationorganization2003Oct 16ISI:000185924500046<Go to ISI>://000185924500046[16]) and both single-gene deletions affect RP transcription similarly ADDIN EN.CITE Rudra20051117Rudra, D.Zhao, Y.Warner, J. R.Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA.
Warner, JR, Albert Einstein Coll Med, Dept Cell Biol, 1300 Morris Pk Ave, Bronx, NY 10461 USA.
warner@aecom.yu.eduCentral role of Ifh1p-Fhl1p interaction in the synthesis of yeast ribosomal proteinsThe EMBO JournalEMBO J.The EMBO JournalEMBO J.The EMBO JournalEMBO J.533-542243chromatinFHA domainribosomal proteinstranscriptionyeastras/cyclic amp pathwaydna-binding domainfork head proteinsaccharomyces-cerevisiaegene-expressiontransactivator potentiationenvironmental-changestranscription factorscrystal-structurecell-cycle2005Feb 9ISI:000227494800009<Go to ISI>://000227494800009Hall20067717Hall, D. B.Wade, J. T.Struhl, K.Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
Struhl, K, Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
kevin@hms.harvard.eduMolecular and Cellular BiologyMol. Cell. Biol.Molecular and Cellular BiologyMol. Cell. Biol.Molecular and Cellular BiologyMol. Cell. Biol.3672-3679269GROUP 1/2 HOMOLOGCHROMOSOMAL-PROTEINSBINDING-SITESBOX PROTEINYEASTRAP1TRANSCRIPTIONEXPRESSIONACTIVATORGENOME2006May0270-7306ISI:000236993300027Article<Go to ISI>://000236993300027 [15,17]. Additional regulators such as Sfp1 and Crf1 can contribute to RP gene regulation via Ifh1 and Fhl1 ADDIN EN.CITE Jorgensen20044417Jorgensen, P.Rupes, I.Sharom, J. R.Schneper, L.Broach, J. R.Tyers, M.Univ Toronto, Dept Med Genet & Microbiol, Toronto, ON M5S 1A8, Canada. Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. Princeton Univ, Dept Biol Mol, Princeton, NJ 08544 USA.
Tyers, M, Univ Toronto, Dept Med Genet & Microbiol, 100 Coll St, Toronto, ON M5S 1A8, Canada.
tyers@mshri.on.caA dynamic transcriptional network communicates growth potential to ribosome synthesis and critical cell sizeGenes & DevelopmentGenes Dev.Genes & DevelopmentGenes Dev.Genes & DevelopmentGenes Dev.2491-25051820ribosomenutrientsnucleolussizestartyeast saccharomyces-cerevisiaefork head proteingene-expressionbudding yeastnutrient availabilityregulatory networkssignalingpathwaygenomic scalerna synthesiscycle2004Oct 15ISI:000224514200007<Go to ISI>://000224514200007Martin2004121217Martin, D. E.Soulard, A.Hall, M. N.Univ Basel, Biozentrum, Div Biochem, CH-4056 Basel, Switzerland.
Hall, MN, Univ Basel, Biozentrum, Div Biochem, Klingelbergstr 70, CH-4056 Basel, Switzerland.
m.hall@unibas.chTOR regulates ribosomal protein gene expression via PKA and the forkhead transcription factor FHL1CellCellCellCellCellCell969-9791197rna-polymerase-isaccharomyces-cerevisiaesignaling pathwaycell-growthfha domainmass-spectrometryhead proteinyeastrapamycinrecruitment2004Dec 29ISI:000226109700009<Go to ISI>://000226109700009Zhao2006222217Zhao, Y.McIntosh, K. B.Rudra, D.Schawalder, S.Shore, D.Warner, J. R.Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA. Univ Genoa, Dept Mol Biol, CH-1211 Geneva 4, Switzerland. Univ Genoa, NCCR Program Frontiers Genet, CH-1211 Geneva 4, Switzerland.
Warner, JR, Albert Einstein Coll Med, Dept Cell Biol, 1300 Morris Pk Ave, Bronx, NY 10461 USA.
warner@aecom.yu.eduFine-structure analysis of ribosomal protein gene transcriptionMolecular and Cellular BiologyMol. Cell. Biol.Molecular and Cellular BiologyMol. Cell. Biol.Molecular and Cellular BiologyMol. Cell. Biol.4853-48622613REPRESSOR-ACTIVATOR PROTEIN-1FORK HEAD PROTEINSACCHAROMYCES-CEREVISIAEGENOME-WIDEYEASTEXPRESSIONRECRUITMENTBINDINGRAP1PPROMOTER2006Jul0270-7306ISI:000238507800009Article<Go to ISI>://000238507800009 [5,18,19], but these effects are probably indirect ADDIN EN.CITE Cipollina200821921917Cipollina, Chiaravan den Brink, JoostDaran-Lapujade, PascalePronk, Jack T.Vai, Marinade Winde, Johannes H.Revisiting the role of yeast Sfp1 in ribosome biogenesis and cell size control: a chemostat studyMicrobiologyMicrobiologyMicrobiologyMicrobiology337-34615412008January 1, 2008http://mic.sgmjournals.org/cgi/content/abstract/154/1/337 10.1099/mic.0.2007/011767-0[20] or strain-specific (Crf1). Sch9mediated regulation affects RP gene expression in the same qualitative fashion as Ifh1, but the mechanism of action is unknown ADDIN EN.CITE Jorgensen20044417Jorgensen, P.Rupes, I.Sharom, J. R.Schneper, L.Broach, J. R.Tyers, M.Univ Toronto, Dept Med Genet & Microbiol, Toronto, ON M5S 1A8, Canada. Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. Princeton Univ, Dept Biol Mol, Princeton, NJ 08544 USA.
Tyers, M, Univ Toronto, Dept Med Genet & Microbiol, 100 Coll St, Toronto, ON M5S 1A8, Canada.
tyers@mshri.on.caA dynamic transcriptional network communicates growth potential to ribosome synthesis and critical cell sizeGenes & DevelopmentGenes Dev.Genes & DevelopmentGenes Dev.Genes & DevelopmentGenes Dev.2491-25051820ribosomenutrientsnucleolussizestartyeast saccharomyces-cerevisiaefork head proteingene-expressionbudding yeastnutrient availabilityregulatory networkssignalingpathwaygenomic scalerna synthesiscycle2004Oct 15ISI:000224514200007<Go to ISI>://000224514200007Rudra20051117Rudra, D.Zhao, Y.Warner, J. R.Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA.
Warner, JR, Albert Einstein Coll Med, Dept Cell Biol, 1300 Morris Pk Ave, Bronx, NY 10461 USA.
warner@aecom.yu.eduCentral role of Ifh1p-Fhl1p interaction in the synthesis of yeast ribosomal proteinsThe EMBO JournalEMBO J.The EMBO JournalEMBO J.The EMBO JournalEMBO J.533-542243chromatinFHA domainribosomal proteinstranscriptionyeastras/cyclic amp pathwaydna-binding domainfork head proteinsaccharomyces-cerevisiaegene-expressiontransactivator potentiationenvironmental-changestranscription factorscrystal-structurecell-cycle2005Feb 9ISI:000227494800009<Go to ISI>://000227494800009[17,18]. However, experiments suggest that regulated binding of Ifh1 is the predominant mode of controlling promoter activity ADDIN EN.CITE Wade20048817Wade, J. T.Hall, D. B.Struhl, K.Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
Struhl, K, Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
kevin@hms.harvard.eduThe transcription factor Ifh1 is a key regulator of yeast ribosomal protein genesNatureNatureNatureNatureNatureNature1054-10584327020FORK HEAD PROTEINSACCHAROMYCES-CEREVISIAEBINDING-SITESEXPRESSIONRAP1PROMOTERSEQUENCEASSOCIATIONRECRUITMENTACTIVATOR2004Dec0028-0836ISI:000225887000048Article<Go to ISI>://000225887000048 Schawalder20045517Schawalder, S. B.Kabani, M.Howald, I.Choudhury, U.Werner, M.Shore, D.Univ Geneva, Dept Mol Biol, CH-1211 Geneva 4, Switzerland. Univ Geneva, NCCR Program Frontiers Genet, CH-1211 Geneva, Switzerland. CEA Saclay, Serv Biochim & Genet Mol, F-91191 Gif Sur Yvette, France.
Shore, D, Univ Geneva, Dept Mol Biol, Sci 3,30 Quai Ernest Ansermet, CH-1211 Geneva 4, Switzerland.
David.Shore@molbio.unige.chGrowth-regulated recruitment of the essential yeast ribosomal protein gene activator Ifh1NatureNatureNatureNatureNatureNature1058-10614327020genome-wide locationfork head proteinsaccharomyces-cerevisiaeenvironmental-changesexpressionpathwayrap1bindingfhl12004Dec 23ISI:000225887000049<Go to ISI>://000225887000049[12,13]. Therefore, a model comprising only the molecules Rap1 (representing the functionally equivalent GRFs Rap1, Abf1, and Reb1), Fhl1 (representing Fhl1 and Hmo1), and Ifh1 is expected to capture key aspects of transcriptional control of RP genes.
Model Reactions and Kinetics
Elementary binding steps in the assembly of transcription factors at the ribosomal protein gene (RPGene) promoter were assumed to follow massaction laws ADDIN EN.CITE Horn197223423417Horn, F.Jackson, R.General Mass Action KineticsArchive for Rational Mechanics and AnalysisArch. Rational Mech. Anal.Archive for Rational Mechanics and AnalysisArch. Rational Mech. Anal.Archive for Rational Mechanics and AnalysisArch. Rational Mech. Anal.81-&4721972WOS:A1972N602600001<Go to ISI>://WOS:A1972N602600001 Feinberg197223323317Feinberg, M.Chemical-Kinetics of a Certain ClassArchive for Rational Mechanics and AnalysisArch. Rational Mech. Anal.Archive for Rational Mechanics and AnalysisArch. Rational Mech. Anal.Archive for Rational Mechanics and AnalysisArch. Rational Mech. Anal.1-&46119720003-9527ISI:A1972N000900001Article<Go to ISI>://A1972N000900001 [21,22]. Net association kinetics of two generic molecules Ai and Bi reacting according to
EMBED Equation.DSMT4 MACROBUTTON MTPlaceRef \* MERGEFORMAT SEQ MTEqn \h \* MERGEFORMAT ( SEQ MTEqn \c \* Arabic \* MERGEFORMAT 1)
was hence described by
EMBED Equation.DSMT4 MACROBUTTON MTPlaceRef \* MERGEFORMAT SEQ MTEqn \h \* MERGEFORMAT ( SEQ MTEqn \c \* Arabic \* MERGEFORMAT 2)
where square brackets indicate the (nuclear) concentration of the relevant species. The ( in between the species names indicates formation of a protein-protein or proteinDNA complex. From this representation, the equilibrium binding constants Ki were directly inferred for all i binding steps:
EMBED Equation.DSMT4 MACROBUTTON MTPlaceRef \* MERGEFORMAT SEQ MTEqn \h \* MERGEFORMAT ( SEQ MTEqn \c \* Arabic \* MERGEFORMAT 3)
We assumed constant total concentrations of all species promoter and transcription factors. The following lists of reactions provide details for all models considered, including the assignment of kinetic parameters:
Model 1
EMBED Equation.DSMT4 MACROBUTTON MTPlaceRef \* MERGEFORMAT SEQ MTEqn \h \* MERGEFORMAT ( SEQ MTEqn \c \* Arabic \* MERGEFORMAT 4)
EMBED Equation.DSMT4 MACROBUTTON MTPlaceRef \* MERGEFORMAT SEQ MTEqn \h \* MERGEFORMAT ( SEQ MTEqn \c \* Arabic \* MERGEFORMAT 5)
EMBED Equation.DSMT4 MACROBUTTON MTPlaceRef \* MERGEFORMAT SEQ MTEqn \h \* MERGEFORMAT ( SEQ MTEqn \c \* Arabic \* MERGEFORMAT 6)
EMBED Equation.DSMT4 MACROBUTTON MTPlaceRef \* MERGEFORMAT SEQ MTEqn \h \* MERGEFORMAT ( SEQ MTEqn \c \* Arabic \* MERGEFORMAT 7)
Model 2
EMBED Equation.DSMT4 MACROBUTTON MTPlaceRef \* MERGEFORMAT SEQ MTEqn \h \* MERGEFORMAT ( SEQ MTEqn \c \* Arabic \* MERGEFORMAT 8)
EMBED Equation.DSMT4 MACROBUTTON MTPlaceRef \* MERGEFORMAT SEQ MTEqn \h \* MERGEFORMAT ( SEQ MTEqn \c \* Arabic \* MERGEFORMAT 9)
EMBED Equation.DSMT4 MACROBUTTON MTPlaceRef \* MERGEFORMAT SEQ MTEqn \h \* MERGEFORMAT ( SEQ MTEqn \c \* Arabic \* MERGEFORMAT 10)
EMBED Equation.DSMT4 MACROBUTTON MTPlaceRef \* MERGEFORMAT SEQ MTEqn \h \* MERGEFORMAT ( SEQ MTEqn \c \* Arabic \* MERGEFORMAT 11)
Model 3
EMBED Equation.DSMT4 MACROBUTTON MTPlaceRef \* MERGEFORMAT SEQ MTEqn \h \* MERGEFORMAT ( SEQ MTEqn \c \* Arabic \* MERGEFORMAT 12)
EMBED Equation.DSMT4 MACROBUTTON MTPlaceRef \* MERGEFORMAT SEQ MTEqn \h \* MERGEFORMAT ( SEQ MTEqn \c \* Arabic \* MERGEFORMAT 13)
EMBED Equation.DSMT4 MACROBUTTON MTPlaceRef \* MERGEFORMAT SEQ MTEqn \h \* MERGEFORMAT ( SEQ MTEqn \c \* Arabic \* MERGEFORMAT 14)
Model 4
EMBED Equation.DSMT4 MACROBUTTON MTPlaceRef \* MERGEFORMAT SEQ MTEqn \h \* MERGEFORMAT ( SEQ MTEqn \c \* Arabic \* MERGEFORMAT 15)
Gene Silencing
When considering gene silencing, we added a single reaction to each promoter model. Unspecific chromatin remodeling was represented by simple first-order reactions converting an active gene (RPGene) into the inactive form (RPGenein) and vice versa:
EMBED Equation.DSMT4 MACROBUTTON MTPlaceRef \* MERGEFORMAT SEQ MTEqn \h \* MERGEFORMAT ( SEQ MTEqn \c \* Arabic \* MERGEFORMAT 16)
Promoter Activity and Transcriptional Efficiencies
The resulting relative transcriptional activity of the promoter was calculated as the sum of the concentrations of all promoter complexes with transcriptional activity. Fullyassembled promoter complexes were assigned a transcriptional efficiency of h = 1 . 0 ( h ( [ 0 , 1 ] ) , w h e r e t h e d e f i n i t i o n o f f u l l y a s s e m b l e d w a s m o d e l - d e p e n d e n t ( c f . R E F _ R e f 1 7 3 3 4 0 4 4 3 \ h T a b l e S 1 T a b l e S 1 ) . I n t h i s w a y , t h e m a x i m u m t h e o r e t i c a l a c t i v i t y w a s a c h i e v e d w h e n t h e c o n c e n t r a t i o n o f f u l l y a s s e m b l e d p r o m o t e r s w a s i d e n t i c a l t o t h e t o t a l p r o m o t e r c o n c e n t r a t i o n . W e r e p r e s e n t e d b a s a l a c t i v i t y c o n v e y e d b y R a p 1 2 ( R P G e n e c o m p l e x e s b y c h o o s i n g l o w v a l u e s o f h: D e p e n d i n g o n t h e a n a l y s i s p e r f o r m e d , hb a s a l w a s s e t t o e i t h e r 0 . 0 5 ( d e f a u l t ) o r 0 . 2 w h e r e s t a t e d e x p l i c i t l y . A s s i g n m e n t o f 5 % b a s a l a c t i v i t y w a s b a s e d o n t h e o b s e r v a t i o n t h a t r i b o s o m e s a r e s y n t h e s i z e d a t a b o u t 5 - 1 0 % o f t h e n o r m a l r a t e i n f h l 1 D m u t a n t s A D D I N E N . C I T E <