No retraction, correction or concern found when last checked on Nov 4, 2026.
Promoters maintain their relative activity levels under different growth conditions
Leeat Keren, Ora Zackay, Maya Lotan‐Pompan and 10 more
Molecular Systems Biology · 2013 · CC BY-NC-SA
Abstract
Most genes change expression levels across conditions, but it is unclear which of these changes represents specific regulation and what determines their quantitative degree. Here, we accurately measured activities of ~900 S. cerevisiae and ~1800 E. coli promoters using fluorescent reporters. We show that in both organisms 60-90% of promoters change their expression between conditions by a constant global scaling factor that depends only on the conditions and not on the promoter's identity. Quantifying such global effects allows precise characterization of specific regulation-promoters deviating from the global scale line. These are organized into few functionally related groups that also adhere to scale lines and preserve their relative activities across conditions. Thus, only several scaling factors suffice to accurately describe genome-wide expression profiles across conditions. We present a parameter-free passive resource allocation model that quantitatively accounts for the global scaling factors. It suggests that many changes in expression across conditions result from global effects and not specific regulation, and provides means for quantitative interpretation of expression profiles.
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References 84
- 1.
Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, Harris MA, Hill DP, Issel-Tarver L, Kasarskis A, Lewis S, Matese JC, Richardson JE, Ringwald M, Rubin GM, Sherlock G (2000 ) Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet 25: 25–29
Not in our library10.1038/75556
- 2.
Badis G, Chan ET, van Bakel H, Pena-Castillo L, Tillo D, Tsui K, Carlson CD, Gossett AJ, Hasinoff MJ, Warren CL, Gebbia M, Talukder S, Yang A, Mnaimneh S, Terterov D, Coburn D, Li Yeo A, Yeo ZX, Clarke ND, Lieb JD (2008 ) A library of yeast transcription factor motifs reveals a widespread function for Rsc3 in targeting nucleosome exclusion at promoters. Mol Cell 32: 878–887
Not in our library10.1016/j.molcel.2008.11.020
- 3.
Bakel H Van, Holstege FCP (2008 ) A tutorial for DNA microarray expression profiling. Cell Evaluating: 22–28, Available at: http://download.cell.com/images/edimages/etbr/VANBAKEL.PDF
Not in our library
- 4.
Balázsi G, Oltvai ZN (2007 ) A pitfall in series of microarrays: the position of probes affects the cross-correlation of gene expression profiles. Methods Mol Biol (Clifton, NJ) 377: 153–162
Not in our library10.1007/978-1-59745-390-5_9
- 5.
Bammler T, Beyer RP, Bhattacharya S, Boorman GA, Boyles A, Bradford BU, Bumgarner RE, Bushel PR, Chaturvedi K, Choi D, Cunningham ML, Deng S, Dressman HK, Fannin RD, Farin FM, Freedman JH, Fry RC, Harper A, Humble MC, Hurban P (2005 ) Standardizing global gene expression analysis between laboratories and across platforms. Nat Meth 2: 351–356
Not in our library10.1038/nmeth754
- 6.
Benjamini Y, Hochberg Y (1995 ) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Series B Methodol 57: 289–300
Not in our library
- 7.
Boer VM, de Winde JH, Pronk JT, Piper MDW (2003 ) The genome-wide transcriptional responses of Saccharomyces cerevisiae grown on glucose in aerobic chemostat cultures limited for carbon, nitrogen, phosphorus, or sulfur. J Biol Chem 278: 3265–3274
Not in our library10.1074/jbc.m209759200
- 8.
Brauer MJ, Huttenhower C, Airoldi EM, Rosenstein R, Matese JC, Gresham D, Boer VM, Troyanskaya OG, Botstein D (2008 ) Coordination of growth rate, cell cycle, stress response, and metabolic activity in yeast. Mol Biol Cell 19: 352–367
Not in our library10.1091/mbc.e07-08-0779
- 9.
Bremer H, Dennis P (1987 ) Modulation of chemical composition and other parameters of the cell by growth rate. Escherichia coli and Salmonella. Available at: http://ctbp.ucsd.edu/qbio/beemer96.pdf [Accessed 7 November 2011]
Not in our library
- 10.
Broach JR (2012 ) Nutritional control of growth and development in yeast. Genetics 192: 73–105
Not in our library10.1534/genetics.111.135731
- 11.
Bronstein I, Fortin J, Stanley PE, Stewart GS, Kricka LJ (1994 ) Chemiluminescent and bioluminescent reporter gene assays. Anal Biochem 219: 169–181
Not in our library10.1006/abio.1994.1254
- 12.
- 13.
Chechik G, Oh E, Rando O, Weissman J, Regev A, Koller D (2008 ) Activity motifs reveal principles of timing in transcriptional control of the yeast metabolic network. Nat Biotechnol 26: 1251–1259
Not in our library10.1038/nbt.1499
- 14.
Churchill GA (2002 ) Fundamentals of experimental design for cDNA microarrays. Nat Genet 32(Suppl): 490–495
Not in our library10.1038/ng1031
- 15.
Cormack BP, Valdivia RH, Falkow S (1996 ) FACS-optimized mutants of the green fluorescent protein (GFP). Gene 173: 33–38
Not in our library10.1016/0378-1119(95)00685-0
- 16.
Costenoble R, Picotti P, Reiter L, Stallmach R, Heinemann M, Sauer U, Aebersold R (2011 ) Comprehensive quantitative analysis of central carbon and amino-acid metabolism in Saccharomyces cerevisiae under multiple conditions by targeted proteomics. Mol Syst Biol 7: 464
Not in our library10.1038/msb.2010.122
- 17.
Cox RS, Surette MG, Elowitz MB (2007 ) Programming gene expression with combinatorial promoters. Mol Syst Biol 3: 145
Not in our library10.1038/msb4100187
- 18.
De Godoy LMF, Olsen J V, Cox J, Nielsen ML, Hubner NC, Fröhlich F, Walther TC, Mann M (2008 ) Comprehensive mass-spectrometry-based proteome quantification of haploid versus diploid yeast. Nature 455: 1251–1254
Not in our library10.1038/nature07341
- 19.
DeRisi JL (1997 ) Exploring the metabolic and genetic control of gene expression on a genomic scale. Science 278: 680–686
Not in our library10.1126/science.278.5338.680
- 20.
- 21.
Edgar R (2002 ) Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res 30: 207–210
Not in our library10.1093/nar/30.1.207
- 22.
Ehrenberg M, Kurland CG (1984 ) Costs of accuracy determined by a maximal growth rate constraint. Q Rev Biophys 17: 45–82
Not in our library10.1017/s0033583500005254
- 23.
Fazio A, Jewett M (2008 ) Transcription factor control of growth rate dependent genes in Saccharomyces cerevisiae: a three factor design. BMC Available at: http://www.biomedcentral.com/1471-2164/9/341 [Accessed 7 November 2011]
Not in our library10.1186/1471-2164-9-341
- 24.
Fendt S-M, Sauer U (2010 ) Transcriptional regulation of respiration in yeast metabolizing differently repressive carbon substrates. BMC Syst Biol 4: 12
Not in our library10.1186/1752-0509-4-12
- 25.
Frantz S (2005 ) An array of problems. Nat Rev Drug Discov 4: 362–363
Not in our library10.1038/nrd1746
- 26.
Gasch AP, Eisen MB (2002 ) Exploring the conditional coregulation of yeast gene expression through fuzzy k-means clustering. Genome Biol 3: RESEARCH0059
Not in our library10.1186/gb-2002-3-11-research0059
- 27.
Gasch AP, Huang M, Metzner S, Botstein D, Elledge SJ, Brown PO (2001 ) Genomic expression responses to DNA-damaging agents and the regulatory role of the yeast ATR homolog Mec1p. Mol Biol Cell 12: 2987–3003
Not in our library10.1091/mbc.12.10.2987
- 28.
- 29.
- 30.
Gertz J, Siggia ED, Cohen BA (2009 ) Analysis of combinatorial cis-regulation in synthetic and genomic promoters. Nature 457: 215–218
Not in our library10.1038/nature07521
- 31.
Ghaemmaghami S, Huh W-K, Bower K, Howson RW, Belle A, Dephoure N, O’Shea EK, Weissman JS (2003 ) Global analysis of protein expression in yeast. Nature 425: 737–741
Not in our library10.1038/nature02046
- 32.
Haurie V, Perrot M, Mini T, Jenö P, Sagliocco F, Boucherie H (2001 ) The transcriptional activator Cat8p provides a major contribution to the reprogramming of carbon metabolism during the diauxic shift in Saccharomyces cerevisiae. J Biol Chem 276: 76–85
Not in our library10.1074/jbc.m008752200
- 33.
Holstege FC, Jennings EG, Wyrick JJ, Lee TI, Hengartner CJ, Green MR, Golub TR, Lander ES, Young RA (1998 ) Dissecting the regulatory circuitry of a eukaryotic genome. Cell 95: 717–728
Not in our library10.1016/s0092-8674(00)81641-4
- 34.
Hughes JD, Estep PW, Tavazoie S, Church GM (2000 ) Computational identification of cis-regulatory elements associated with groups of functionally related genes in Saccharomyces cerevisiae. J Mol Biol 296: 1205–1214
Not in our library10.1006/jmbi.2000.3519
- 35.
Huisinga KL, Pugh BF (2004 ) A genome-wide housekeeping role for TFIID and a highly regulated stress-related role for SAGA in Saccharomyces cerevisiae. Mol Cell 13: 573–585
Not in our library10.1016/s1097-2765(04)00087-5
- 36.
Ihmels J, Friedlander G, Bergmann S, Sarig O, Ziv Y, Barkai N (2002 ) Revealing modular organization in the yeast transcriptional network. Nat Genet 31: 370–377
Not in our library10.1038/ng941
- 37.
Ingraham JL, Maaløe O, Neidhardt FC (1983 ) Growth of the Bacterial Cell Sunderland, MA: Sinauer Assoc.,
Not in our library
- 38.
Islam S, Kjällquist U, Moliner A, Zajac P, Fan J-B, Lönnerberg P, Linnarsson S (2011 ) Characterization of the single-cell transcriptional landscape by highly multiplex RNA-seq. Genome Res 21: 1160–1167
Not in our library10.1101/gr.110882.110
- 39.
Jacob F, Monod J (1961 ) Genetic regulatory mechanisms in the synthesis of proteins. J Mol Biol 3: 318–356
Not in our library10.1016/s0022-2836(61)80072-7
- 40.
Kalir S, McClure J, Pabbaraju K, Southward C, Ronen M, Leibler S, Surette MG, Alon U (2001 ) Ordering genes in a flagella pathway by analysis of expression kinetics from living bacteria. Science (New York, NY) 292: 2080–2083
Not in our library10.1126/science.1058758
- 41.
Klumpp S, Hwa T (2008 ) Growth-rate-dependent partitioning of RNA polymerases in bacteria. Proc Natl Acad Sci USA 105: 20245–20250
Not in our library10.1073/pnas.0804953105
- 42.
Klumpp S, Zhang Z, Hwa T (2009 ) Growth rate-dependent global effects on gene expression in bacteria. Cell 139: 1366–1375
Not in our library10.1016/j.cell.2009.12.001
- 43.
Koch AL (1988 ) Why can’t a cell grow infinitely fast? Can J Microbiol 34: 421–426
Not in our library10.1139/m88-074
- 44.
Lai L-C, Kosorukoff AL, Burke P V, Kwast KE (2005 ) Dynamical remodeling of the transcriptome during short-term anaerobiosis in Saccharomyces cerevisiae: differential response and role of Msn2 and/or Msn4 and other factors in galactose and glucose media. Mol Cell Biol 25: 4075–4091
Not in our library10.1128/mcb.25.10.4075-4091.2005
- 45.
Levy S, Barkai N (2009 ) Coordination of gene expression with growth rate: a feedback or a feed-forward strategy? FEBS Lett 583: 3974–3978
Not in our library10.1016/j.febslet.2009.10.071
- 46.
Ligr M, Siddharthan R, Cross FR, Siggia ED (2006 ) Gene expression from random libraries of yeast promoters. Genetics 172: 2113–2122
Not in our library10.1534/genetics.105.052688
- 47.
Lipson D, Raz T, Kieu A, Jones DR, Giladi E, Thayer E, Thompson JF, Letovsky S, Milos P, Causey M (2009 ) Quantification of the yeast transcriptome by single-molecule sequencing. Nat Biotechnol 27: 652–658
Not in our library10.1038/nbt.1551
- 48.
Lovén J, Orlando DA, Sigova AA, Lin CY, Rahl PB, Burge CB, Levens DL, Lee TI, Young RA (2012 ) Revisiting global gene expression analysis. Cell 151: 476–482
Not in our library10.1016/j.cell.2012.10.012
- 49.
Maaloe O (1969 ) An analysis of bacterial growth. Dev Biol 3: 33–58
Not in our library
- 50.
Magnusson LU, Farewell A, Nyström T (2005 ) ppGpp: a global regulator in Escherichia coli. Trends Microbiol 13: 236–242
Not in our library10.1016/j.tim.2005.03.008
- 51.
Marshall E (2004 ) Getting the noise out of gene arrays. Science (New York, NY) 306: 630–631
Not in our library10.1126/science.306.5696.630
- 52.
Molenaar D, van Berlo R, de Ridder D, Teusink B (2009 ) Shifts in growth strategies reflect tradeoffs in cellular economics. Mol Syst Biol 5: 323
Not in our library10.1038/msb.2009.82
- 53.
Murphy KF, Balázsi G, Collins JJ (2007 ) Combinatorial promoter design for engineering noisy gene expression. Proc Natl Acad Sci USA 104: 12726–12731
Not in our library10.1073/pnas.0608451104
- 54.
Nagalakshmi U, Wang Z, Waern K, Shou C, Raha D, Gerstein M, Snyder M (2008 ) The transcriptional landscape of the yeast genome defined by RNA sequencing. Science (New York, NY) 320: 1344–1349
Not in our library10.1126/science.1158441
- 55.
Neidhardt FC (1999 ) Bacterial growth: constant obsession with dN/dt. J Bacteriol 181: 7405–7408
Not in our library10.1128/jb.181.24.7405-7408.1999
- 56.
Newman JRS, Ghaemmaghami S, Ihmels J, Breslow DK, Noble M, DeRisi JL, Weissman JS (2006 ) Single-cell proteomic analysis of S. cerevisiae reveals the architecture of biological noise. Nature 441: 840–846
Not in our library10.1038/nature04785
- 57.
- 58.
O’Rourke SM, Herskowitz I (2002 ) A third osmosensing branch in Saccharomyces cerevisiae requires the Msb2 protein and functions in parallel with the Sho1 branch. Mol Cell Biol 22: 4739–4749
Not in our library10.1128/mcb.22.13.4739-4749.2002
- 59.
Pedersen S, Bloch PL, Reeh S, Neidhardt FC (1978 ) Patterns of protein synthesis in E. coli: a catalog of the amount of 140 individual proteins at different growth rates. Cell 14: 179–190
Not in our library10.1016/0092-8674(78)90312-4
- 60.
Raveh-Sadka T, Levo M, Shabi U, Shany B, Keren L, Lotan-Pompan M, Zeevi D, Sharon E, Weinberger A, Segal E (2012 ) Manipulating nucleosome disfavoring sequences allows fine-tune regulation of gene expression in yeast. Nat Genet 44: 743–750
Not in our library10.1038/ng.2305
- 61.
- 62.
Saldanha AJ, Brauer MJ, Botstein D (2004 ) Nutritional homeostasis in batch and steady-state culture of yeast. Mol Biol Cell 15: 4089–4104
Not in our library10.1091/mbc.e04-04-0306
- 63.
Schaechter M (1958 ) Dependency on medium and temperature of cell size and chemical composition during balanced growth of Salmonella typhimurium. J Gen Microbiol 19: 592–606
Not in our library10.1099/00221287-19-3-592
- 64.
Scott M, Gunderson CW, Mateescu EM, Zhang Z, Hwa T (2010 ) Interdependence of cell growth and gene expression: origins and consequences. Science (New York, NY) 330: 1099–1102
Not in our library10.1126/science.1192588
- 65.
Segal E, Shapira M, Regev A, Pe’er D, Botstein D, Koller D, Friedman N (2003 ) Module networks: identifying regulatory modules and their condition-specific regulators from gene expression data. Nat Genet 34: 166–176
Not in our library10.1038/ng1165
- 66.
Shalem O, Dahan O, Levo M, Martinez MR, Furman I, Segal E, Pilpel Y (2008 ) Transient transcriptional responses to stress are generated by opposing effects of mRNA production and degradation. Mol Syst Biol 4: 223
Not in our library10.1038/msb.2008.59
- 67.
Sharon E, Kalma Y, Sharp A, Raveh-Sadka T, Levo M, Zeevi D, Keren L, Yakhini Z, Weinberger A, Segal E (2012 ) Inferring gene regulatory logic from high-throughput measurements of thousands of systematically designed promoters. Nat Biotechnol 30: 521–530
Not in our library10.1038/nbt.2205
- 68.
Spellman PT, Sherlock G, Zhang MQ, Iyer VR, Anders K, Eisen MB, Brown PO, Botstein D, Futcher B (1998 ) Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization. Mol Biol Cell 9: 3273–3297
Not in our library10.1091/mbc.9.12.3273
- 69.
Stewart-Ornstein J, Weissman JS, El-Samad H (2012 ) Cellular noise regulons underlie fluctuations in Saccharomyces cerevisiae. Mol Cell 45: 483–493
Not in our library10.1016/j.molcel.2011.11.035
- 70.
Tachibana C, Yoo JY, Tagne J-B, Kacherovsky N, Lee TI, Young ET (2005 ) Combined global localization analysis and transcriptome data identify genes that are directly coregulated by Adr1 and Cat8. Mol Cell Biol 25: 2138–2146
Not in our library10.1128/mcb.25.6.2138-2146.2005
- 71.
Tang T, François N, Glatigny A, Agier N, Mucchielli M-H, Aggerbeck L, Delacroix H (2007 ) Expression ratio evaluation in two-colour microarray experiments is significantly improved by correcting image misalignment. Bioinformatics (Oxford, England) 23: 2686–2691
Not in our library10.1093/bioinformatics/btm399
- 72.
Tirosh I, Barkai N (2008 ) Two strategies for gene regulation by promoter nucleosomes. Genome Res 18: 1084–1091
Not in our library10.1101/gr.076059.108
- 73.
Tirosh I, Wong KH, Barkai N, Struhl K (2011 ) Extensive divergence of yeast stress responses through transitions between induced and constitutive activation. Proc Natl Acad Sci USA 108: 16693–16698
Not in our library10.1073/pnas.1113718108
- 74.
Tu BP, Kudlicki A, Rowicka M, McKnight SL (2005 ) Logic of the yeast metabolic cycle: temporal compartmentalization of cellular processes. Science (New York, NY) 310: 1152–1158
Not in our library10.1126/science.1120499
- 75.
Van de Peppel J, Kemmeren P, van Bakel H, Radonjic M, van Leenen D, Holstege FCP (2003 ) Monitoring global messenger RNA changes in externally controlled microarray experiments. EMBO Rep 4: 387–393
Not in our library10.1038/sj.embor.embor798
- 76.
Wade C, Shea KA, Jensen R V, McAlear MA (2001 ) EBP2 is a member of the yeast RRB regulon, a transcriptionally coregulated set of genes that are required for ribosome and rRNA biosynthesis. Mol Cell Biol 21: 8638–8650
Not in our library10.1128/mcb.21.24.8638-8650.2001
- 77.
Wang M, Weiss M, Simonovic M, Haertinger G, Schrimpf SP, Hengartner MO, von Mering C (2012 ) PaxDb, a database of protein abundance averages across all three domains of life. Mol Cell Proteomics 11: 492–500
Not in our library10.1074/mcp.o111.014704
- 78.
Yassour M, Kaplan T, Fraser HB, Levin JZ, Pfiffner J, Adiconis X, Schroth G, Luo S, Khrebtukova I, Gnirke A, Nusbaum C, Thompson D-A, Friedman N, Regev A (2009 ) Ab initio construction of a eukaryotic transcriptome by massively parallel mRNA sequencing. Proc Natl Acad Sci USA 106: 3264–3269
Not in our library10.1073/pnas.0812841106
- 79.
You C, Okano H, Hui S, Zhang Z, Kim M, Gunderson CW, Wang Y-P, Lenz P, Yan D, Hwa T (2013 ) Coordination of bacterial proteome with metabolism by cyclic AMP signalling. Nature 500: 301–306
Not in our library10.1038/nature12446
- 80.
Zaslaver A, Bren A, Ronen M, Itzkovitz S, Kikoin I, Shavit S, Liebermeister W, Surette MG, Alon U (2006 ) A comprehensive library of fluorescent transcriptional reporters for Escherichia coli. Nat Methods 3: 623–628
Not in our library10.1038/nmeth895
- 81.
Zaslaver A, Kaplan S, Bren A, Jinich A, Mayo A, Dekel E, Alon U, Itzkovitz S (2009 ) Invariant distribution of promoter activities in Escherichia coli. PLoS Comput Biol 5: e1000545
Not in our library10.1371/journal.pcbi.1000545
- 82.
Zaslaver A, Mayo AE, Rosenberg R, Bashkin P, Sberro H, Tsalyuk M, Surette MG, Alon U (2004 ) Just-in-time transcription program in metabolic pathways. Nat Genet 36: 486–491
Not in our library10.1038/ng1348
- 83.
Zeevi D, Sharon E, Lotan-Pompan M, Lubling Y, Shipony Z, Raveh-Sadka T, Keren L, Levo M, Weinberger A, Segal E (2011 ) Compensation for differences in gene copy number among yeast ribosomal proteins is encoded within their promoters. Genome Res 21: 2114–2128
Not in our library10.1101/gr.119669.110
- 84.
Zhu C, KJRP Byers, McCord RP, Shi Z, Berger MF, Newburger DE, Saulrieta K, Smith Z, Shah M V, Radhakrishnan M, Philippakis AA, Hu Y, De Masi F, Pacek M, Rolfs A, Murthy T, Labaer J, Bulyk ML (2009 ) High-resolution DNA-binding specificity analysis of yeast transcription factors. Genome Res 19: 556–566
Not in our library10.1101/gr.090233.108
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