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Exploration of Essential Gene Functions via Titratable Promoter Alleles
Open accessAbstract
Nearly 20% of yeast genes are required for viability, hindering genetic analysis with knockouts. We created promoter-shutoff strains for over two-thirds of all essential yeast genes and subjected them to morphological analysis, size profiling, drug sensitivity screening, and microarray expression profiling. We then used this compendium of data to ask which phenotypic features characterized different functional classes and used these to infer potential functions for uncharacterized genes. We identified genes involved in ribosome biogenesis (HAS1, URB1, and URB2), protein secretion (SEC39), mitochondrial import (MIM1), and tRNA charging (GSN1). In addition, apparent negative feedback transcriptional regulation of both ribosome biogenesis and the proteasome was observed. We furthermore show that these strains are compatible with automated genetic analysis. This study underscores the importance of analyzing mutant phenotypes and provides a resource to complement the yeast knockout collection.
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“In general, essential genes participated in ~5-fold more negative and positive interactions than nonessential genes, confirming previous estimates (Fig. 5A)(24).”
From A global genetic interaction network maps a wiring diagram of cellular function (2016) · cites this paper as [24]
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“First, consistent with the results of our previous smaller scale surveys (1, 24), essential genes are major hubs and form the basic scaffold of the global genetic interaction network.”
From A global genetic interaction network maps a wiring diagram of cellular function (2016) · cites this paper as [24]
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“We started with the Yeast Tet-promoters Hughes Collection (yTHC) that is composed of 800 strains; in each strain the endogenous promoter of an essential gene is replaced by a tetracycline promoter (Mnaimneh et al. 2004).”
MethodSynthetic Genetic Array Analysis for Global Mapping of Genetic Networks in Yeast
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Sub1 Functions in Osmoregulation and in Transcription by both RNA Polymerases II and III
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BackgroundA genome-scale CRISPR interference guide library enables comprehensive phenotypic profiling in yeast
McGlincy, N. J., Meacham, Z. A., Reynaud, K., Muller, R. Y., Baum, R., & Ingolia, N. T. (2021) · BMC Genomics · doi:10.1186/s12864-021-07518-0 · Cited by 47
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“Vladimir Lupashin, University of Arkansas for Medical Sciences, USA Daniel Ungar, University of York, UK Frederick Hughson, Princeton University, USA *Correspondence: Mitsuo Tagaya, Department of Molecular Life Sciences, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachio…”
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“Similar strategies have been evolving in parallel in the yeast community, generating digital profiles of phenotypes for large sets of deletions [55,56], titratable alleles [ 57 ], and synthetic lethality between genes [58] or between genes and small molecules [59].”
BackgroundMukherjee, V., Lind, U., St.Onge, R. P., Blomberg, A., & Nygård, Y. (2021) · mSystems · doi:10.1128/msystems.00418-21 · Cited by 41
“expression collections (3, 4), has allowed the construction of yeast regulatory network”
BackgroundMülleder, M., Campbell, K., Matsarskaia, O., Eckerstorfer, F., & Ralser, M. (2016) · F1000Research · doi:10.12688/f1000research.9606.1 · Cited by 39
Prediction of Genetic Interactions Using Machine Learning and Network Properties
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Yeast genetic interaction screens in the age of CRISPR/Cas
Adames, N. R., Gallegos, J. E., & Peccoud, J. (2018) · Current Genetics · doi:10.1007/s00294-018-0887-8 · Cited by 36
Predicting gene targets of perturbations via network-based filtering of mRNA expression compendia
Cosgrove, E. J., Zhou, Y., Gardner, T. S., & Kolaczyk, E. D. (2008) · Bioinformatics · doi:10.1093/bioinformatics/btn476 · Cited by 40
De-Novo Learning of Genome-Scale Regulatory Networks in S. cerevisiae
Ma, S., Kemmeren, P., Gresham, D., & Statnikov, A. (2014) · PLoS ONE · doi:10.1371/journal.pone.0106479 · Cited by 39
“Specifically, 1,509 chips with raw data (CEL files) were downloaded from GEO on 08/21/2013.”
InfluentialThe DSL1 Complex: The Smallest but Not the Least CATCHR
Spang, A. (2012) · Traffic · doi:10.1111/j.1600-0854.2012.01362.x · Cited by 39
Contemporary, yeast-based approaches to understanding human genetic variation
Dunham, M. J., & Fowler, D. M. (2013) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2013.10.001 · Cited by 40
Rescuing yeast mutants with human genes
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“A collection of 602 strains each with a tetO7 promoter substitution was produced by a North American consortium [10].”
BackgroundMethodWang, H., Wang, K., Du, Q., Wang, Y., Fu, Z., Guo, Z., Kang, D., Li, W., & Tang, J. (2018) · New Phytologist · doi:10.1111/nph.15057 · Cited by 39
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Esf2p, a U3-Associated Factor Required for Small-Subunit Processome Assembly and Compaction
Hoang, T., Peng, W., Vanrobays, E., Krogan, N. J., Hiley, S. L., Beyer, A. L., Osheim, Y. N., Greenblatt, J., Hughes, T. R., & Lafontaine, D. L. J. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.13.5523-5534.2005 · Cited by 41
“Since Esf2p is an essential gene (34), our functional analysis used a Tet-regulated allele (tet::esf2) ( 32 , 37) in which ESF2 was placed under the control of a Tet-regulatable promoter, allowing specific transcriptional shutoff upon the addition of doxycycline to the growth medium (see Materials and Methods).”
BackgroundMethodInfluentialSelf-citationFungal resilience and host–pathogen interactions: Future perspectives and opportunities
Brown, A. J. P. (2022) · Parasite Immunology · doi:10.1111/pim.12946 · Cited by 41
A small molecule‐directed approach to control protein localization and function
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Boorsma, A., Lu, X., Zakrzewska, A., Klis, F. M., & Bussemaker, H. J. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003112 · Cited by 38
“We analyzed a wide variety of experiments, including cell cycle [26], various stress response time courses [27], and a collection of gene deletion and gene suppression experiments [28,29]; see Materials and Methods and Supplementary Figure S1 for details.”
BackgroundChemical-genetic approaches for exploring the mode of action of natural products
López, A., Parsons, A. B., Nislow, C., Giaever, G. N., & Boone, C. M. (2008) · Birkhäuser Basel eBooks · doi:10.1007/978-3-7643-8595-8_5 · Cited by 39
Self-citationNucleocytoplasmic Trafficking of the Molecular Chaperone Hsp104 in Unstressed and Heat‐Shocked Cells
Tkach, J. M., & Glover, J. R. (2007) · Traffic · doi:10.1111/j.1600-0854.2007.00666.x · Cited by 38
“DF5 DF5 MATa ura3-52 his3D200 trp1-1leu2-3,11 lys2-801 (34) kap121-34 DF5 MATa ura3-52 his3D200 trp1-1 leu2-3,112 lys2-801 kap121::ura::HIS3 [pkap121-34 TRP1] (34) kap95-14 DF5 MATa ura3-52 his3D200 trp1-1 leu2-3,112 lys2-801 kap95::ura::HIS3 [pkap95-14 TRP1] (59) kap104-16 DF5 MATa ura3-52 his3D200 trp1-1 leu2-3,112…”
Systematic Identification of Novel, Essential Host Genes Affecting Bromovirus RNA Replication
Gancarz, B., Hao, L., He, Q., Newton, M. A., & Ahlquist, P. (2011) · PLoS ONE · doi:10.1371/journal.pone.0023988 · Cited by 37
“It is important to note for this library that expression levels from the substituted TET promoter are often different than expression levels from the endogenous gene promoter [27].”
BackgroundMethodInfluentialLow escape-rate genome safeguards with minimal molecular perturbation of Saccharomyces cerevisiae
Agmon, N., Tang, Z., Yang, K., Sutter, B. A., Ikushima, S., Cai, Y., Caravelli, K., Martin, J. A., Sun, X., Choi, W. J., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1621250114 · Cited by 38
“To identify potential SG essential genes, we began by identifying the 250 strains from the Yeast Tet-Promoters Hughes Collection annotated as having a “severe” or “very severe” phenotype on doxycycline in a “Tet-OFF” strain background (22).”
Pathak, R., Singh, P., Ananthakrishnan, S., Adamczyk, S., Schimmel, O., & Govind, C. K. (2018) · Genetics · doi:10.1534/genetics.118.300943 · Cited by 37
“…the cultures grown at 25°C to 37°C for ∼1.5 hours prior to induction by SM. Spt16 and Spt6 were depleted in SPT16-TET and SPT6-TET (HUGHES et al. 2000; MNAIMNEH et al. 2004) cells by growing these strains in the presence of 10 μg/ml doxycycline overnight, and sub-culturing the overnight cultures…”
MethodInfluentialKainth, P., Sassi, H. E., Peña‐Castillo, L., Chua, G., Hughes, T. R., & Andrews, B. (2009) · Methods · doi:10.1016/j.ymeth.2009.02.015 · Cited by 34
Self-citationLan, H., Carson, R., Provart, N. J., & Bonner, A. J. (2007) · BMC Bioinformatics · doi:10.1186/1471-2105-8-358 · Cited by 37
Czaja, W., Mao, P., & Smerdon, M. J. (2014) · DNA repair · doi:10.1016/j.dnarep.2014.01.002 · Cited by 36
“For the Tet-off experiments, we used a conditional mutant Tet-STH1 strain, bearing a tetracycline-regulated element (Tet) in the promoter of the STH1 gene [49].”
MethodThe Benefits of Humanized Yeast Models to Study Parkinson’s Disease
Franssens, V., Bynens, T., den Brande, J. V., Vandermeeren, K., Verduyckt, M., & Winderickx, J. (2013) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2013/760629 · Cited by 42
“These include not only comprehensive collections of yeast mutants with gene deletions [14], hypomorphic alleles, and conditionally repressible promoters [15], but also plasmid libraries that allow the study of gene overexpression [16] or systematic localization studies using the yeast GFP-fusion collection [17].”
BackgroundAdvances in fungal chemical genomics for the discovery of new antifungal agents
Xue, A., Robbins, N., & Cowen, L. E. (2020) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.14484 · Cited by 41
Exploring Quantitative Yeast Phenomics with Single-Cell Analysis of DNA Damage Foci
Styles, E. B., Founk, K., Zamparo, L., Sing, T. L., Altintas, D. M., Ribeyre, C., Ribaud, V., Rougemont, J., Mayhew, D. N., Costanzo, M., et al. (2016) · Cell Systems · doi:10.1016/j.cels.2016.08.008 · Cited by 33
“…Saccharomyces cerevisiae, genome-wide collections of haploid viable deletion mutants (Giaever et al., 2002; Winzeler et al., 1999) and mutant strains carrying conditional alleles of essential genes (Kofoed et al., 2015; Li et al., 2011; Mnaimneh et al., 2004) enable systematic genetic analysis.”
BackgroundSelf-citationHeterologous Hsp90 promotes phenotypic diversity through network evolution
Koubková-Yu, T. C.-T., Chao, J.-C., & Leu, J. (2018) · PLoS Biology · doi:10.1371/journal.pbio.2006450 · Cited by 35
An improved auxin-inducible degron system for fission yeast
Zhang, X., Zhao, L., Suo, F., Gao, Y., Wu, Q., Qi, X., & Du, L. (2021) · G3 Genes Genomes Genetics · doi:10.1093/g3journal/jkab393 · Cited by 37
“…include creating temperature-sensitive mutants (Dohmen et al. 1994; Kanemaki et al. 2003; Ben-Aroya et al. 2008), placing a target gene under the control of a repressible promoter (Mnaimneh et al. 2004), and chemically induced alteration of the localization of the gene product (Haruki et al. 2008).”
BackgroundTyers, M. (2004) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2004.09.013 · Cited by 35
Strathern, J. N., Malagón, F., Irvin, J. D., Gotte, D., Shafer, B. K., Kireeva, M. L., Lubkowska, L., Jin, D. J., & Kashlev, M. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.429506 · Cited by 34
Horng, Y., Chang, K.-C., Chien, C., Wei, Y., Sun, Y., & Soo, P. (2009) · Letters in Applied Microbiology · doi:10.1111/j.1472-765x.2009.02772.x · Cited by 34
“However, it has been shown that the limitations of such recombinant E. coli strains are unstable gene transcription, prohibitive price and hypersensitive concentration of inducer (Siegele and Hu 1997; Mnaimneh et al. 2004).”
BackgroundHiley, S. L., Babak, T., & Hughes, T. R. (2005) · Nucleic Acids Research · doi:10.1093/nar/gki608 · Cited by 34
“The wild-type control for tet-promoter strains was R1158 (14); for deletion strains, BY4743 (13).”
BackgroundMethodSelf-citationDhungel, N., & Hopper, A. K. (2012) · Genes & Development · doi:10.1101/gad.183004.111 · Cited by 34
“The resulting fragments containing 59 and 39 flanking sequences of the SEN gene 59 region (carrying the Tet-operon cassette) were integrated, replacing the endogenous 59 region as described in Mnaimneh et al. (2004).”
MethodDual Fatty Acid Elongase Complex Interactions in Arabidopsis
Morineau, C., Gissot, L., Bellec, Y., Hématy, K., Tellier, F., Renne, C., Haslam, R. P., Beaudoin, F., Napier, J. A., & Faure, J. (2016) · PLoS ONE · doi:10.1371/journal.pone.0160631 · Cited by 33
Weber, C., Hartig, A., Hartmann, R. K., & Rossmanith, W. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004506 · Cited by 33
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García‐Martínez, J., Gónzález‐Candelas, F., & Pérez-Ortín, J. E. (2007) · Genome biology · doi:10.1186/gb-2007-8-10-r222 · Cited by 33
“For instance, it has been described that transcriptional regulation (both TR and RS) controls the genes of the proteasome and 90S processosome [37].”
BackgroundInferring condition‐specific transcription factor function from DNA binding and gene expression data
McCord, R. P., Berger, M. F., Philippakis, A., & Bulyk, M. L. (2007) · Molecular Systems Biology · doi:10.1038/msb4100140 · Cited by 31
“…and include 650 environmental stresses and perturbations, as well as 407 deletion, 215 titratable promoter, and 55 overexpressor strains (Ihmels et al , 2004; Mnaimneh et al , 2004; Chua et al , 2006); a list of these 1327 datasets and the full set of expression data are available upon request.”
Auxin‐Inducible Degron System for Depletion of Proteins in Saccharomyces cerevisiae
Shetty, A., Reim, N. I., & Winston, F. (2019) · Current Protocols in Molecular Biology · doi:10.1002/cpmb.104 · Cited by 32
“…used to deplete the gene product, including temperature-sensitive mutations (Costanzo et al., 2016), mechanisms to reduce transcript levels (Breslow et al., 2008; Mnaimneh et al., 2004), and a system to sequester nuclear proteins in the cytoplasm (anchor-away; Haruki, Nishikawa, & Laemmli, 2008).”
BackgroundDynamics of the Putative RNA Helicase Spb4 during Ribosome Assembly in Saccharomyces cerevisiae
García-Gómez, J. J., Lebaron, S., Froment, C., Monsarrat, B., Henry, Y. A. L., & de la Cruz, J. (2011) · Molecular and Cellular Biology · doi:10.1128/mcb.05436-11 · Cited by 32
“It has been clearly demonstrated that the RNA helicases Prp43 and Has1 are required for the synthesis of both 40S and 60S r-subunits (6, 13, 34, 37, 38, 41).”
BackgroundThe roles of 3′-exoribonucleases and the exosome in trypanosome mRNA degradation
Fadda, A. A., Färber, V., Droll, D., & CLAYTON, C. E. (2013) · RNA · doi:10.1261/rna.038430.113 · Cited by 30
“Rapid decay of unstable Leishmania mRNAs bearing a conserved retroposon signature 3′-UTR motif is initiated by a site-specific endonucleolytic cleavage without prior deadenylation.”
BackgroundInfluentialEmergence of the primordial pre-60S from the 90S pre-ribosome
Ismail, S., Flemming, D., Thoms, M., Gomes‐Filho, J. V., Randau, L., Beckmann, R., & Hurt, E. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110640 · Cited by 31
“This revealed a primordial pre-60S particle that is dominated by two scaffoldmodules, Rrp5-Noc1-Noc2 andUrb1Urb2-Nop10-Dbp6-Rsa3, and further distinguished by twoprominent snoRNPs, snR190 and snR37; several poorly characterized RNAhelicases, includingMak5; and theSPOUT-domain-containingmethyltransferase pair Upa1-Upa2.”
BackgroundInfluentialMaking Temperature-Sensitive Mutants
Ben‐Aroya, S., Pan, X., Boeke, J. D., & Hieter, P. (2010) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(10)70008-2 · Cited by 30
Systematic Analysis of Essential Genes Reveals Important Regulators of G Protein Signaling
Cappell, S. D., Baker, R., Skowyra, D., & Dohlman, H. G. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.05.026 · Cited by 30
“This TetO7 promoter library has been used previously to identify new components of the cell division cycle (Yu et al., 2006), translation, and mitochondria import machinery (Mnaimneh et al., 2004).”
BackgroundMethodSasvári, Z., Lin, W., Inaba, J.-I., Xu, K., Kovalev, N., & Nagy, P. D. (2020) · Journal of Virology · doi:10.1128/jvi.01979-19 · Cited by 30
“Saccharomyces cerevisiae strains BY4741 (MATa his3 1 leu2 0 met15 0 ura3 0) and R1158 (100), BY4741 sac1Δ (BY4741 sac1Δ::kanMX4), BY4741 Lsb6Δ (BY4741 lsb6Δ::kanMX4), TET::PIK1, and TET::STT4 (yTHC library) were obtained from Open Biosystems.”
Power2: The power of yeast genetics applied to the powerhouse of the cell
Rutter, J. P., & Hughes, A. L. (2015) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2014.12.002 · Cited by 30
Lueder, F., & Lithgow, T. J. (2009) · FEBS Letters · doi:10.1016/j.febslet.2009.03.064 · Cited by 30
Candida glabrata : new tools and technologies—expanding the toolkit
Ho, H.-L., & Haynes, K. (2015) · FEMS Yeast Research · doi:10.1093/femsyr/fov066 · Cited by 29
“…C. glabrata Reference Sequenced and annotated genome √ √ Skrzypek and Hirschman (2011); Inglis et al. (2012) Tet-regulatable library of essential genes √ × Mnaimneh et al. (2004) Knockout library of non-essential genes √ Partial collection available (2015) Giaever et al. (2002); Winzeler et al.…”
BackgroundCheng, E., Vaisica, J. A., Ou, J., Baryshnikova, A., Lu, Y. C., Roth, F. P., & Brown, G. W. (2012) · Genetics · doi:10.1534/genetics.112.141051 · Cited by 30
“Comparison of conditional allele screens for genome instability mutants The collection of tetracycline-regulated promoter conditional alleles (Tet alleles) encompasses 773 essential genes (63%), of a total of 1135 that are annotated in the SGD (Mnaimneh et al. 2004; Yu et al. 2006).”
BackgroundMethodInfluentialSaccharomyces cerevisiae Promoter Engineering before and during the Synthetic Biology Era
Feng, X., & Marchisio, M. A. (2021) · Biology · doi:10.3390/biology10060504 · Cited by 31
“[91] analyzed the effect of the changes in the expression profile of almost 700 essential genes in S.”
BackgroundInaba, J.-I., Xu, K., Kovalev, N., Ramanathan, H. N., Roy, C. R., Lindenbach, B. D., & Nagy, P. D. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1911108116 · Cited by 29
“To study if Rab1/Ypt1 affects TBSV replication, we used the TET::YPT1 yeast strain, in which the expression of Ypt1 could be suppressed via addition of doxycycline to the growth media (30).”
MethodG Protein Mono-ubiquitination by the Rsp5 Ubiquitin Ligase
Torres, M. P., Lee, M. J., Ding, F., Purbeck, C., Kuhlman, B. A., Dokholyan, N. V., & Dohlman, H. G. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m809058200 · Cited by 29
From drug to protein: using yeast genetics for high-throughput target discovery
Armour, C. D., & Lum, P. Y. (2005) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2004.12.001 · Cited by 29
“The expression levels of essential genes were lowered conditionally via a titratable promoter [18].”
BackgroundCell Surface Interference with Plasma Membrane and Transport Processes in Yeasts
François, J. (2015) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-25304-6_2 · Cited by 29
Metabolic regulation of telomere silencing by SESAME complex-catalyzed H3T11 phosphorylation
Zhang, S., Yu, X., Zhang, Y., Xue, X., Yu, Q., Zha, Z., Gogol, M., Workman, J. L., & Li, S. (2021) · Nature Communications · doi:10.1038/s41467-020-20711-1 · Cited by 28
Elucidating regulatory mechanisms downstream of a signaling pathway using informative experiments
Szczurek, E., Gat‐Viks, I., Tiuryn, J., & Vingron, M. (2009) · Molecular Systems Biology · doi:10.1038/msb.2009.45 · Cited by 28
Hull, R. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-384871-0.00007-8 · Cited by 28
“• Various libraries are available including: deletion libraries (YKO) covering most non-essential genes greatly facilitating genome-wide studies of gene functions (Tong et al., 2001; Ammar et al., 2009) ; the down-regulatable essential-gene library (yTHC) (Mnaimneh et al., 2004; Servienne et al., 2006) ; libraries of…”
BackgroundA High‐Throughput Approach for Studying Virus Replication in Yeast
Pogany, J., Panavas, T., Servienė, E., Nawaz‐ul‐Rehman, M. S., & Nagy, P. D. (2010) · Current Protocols in Microbiology · doi:10.1002/9780471729259.mc16j01s19 · Cited by 27
“Model hosts, such as yeast, can be very valuable in identifying the host factors and studying their functional interactions with viral proteins and nucleic acids (Ahlquist et al., 2003; Kushner et al., 2003; Panavas et al., 2005b; Serviene et al., 2005; Nagy and Pogany, 2006; Nagy, 2008).”
BackgroundSvensson, J. P., Pesudo, L. Q., Fry, R. C., Adeleye, Y. A., Carmichael, P. L., & Samson, L. D. (2011) · BMC Systems Biology · doi:10.1186/1752-0509-5-157 · Cited by 26
“The subset of essential genes is more highly conserved between species [17] and may therefore be of more relevance in understanding how humans react to toxicants.”
BackgroundWang, J., Zhao, P., Cheng, B., Zhang, Y., Shen, Y., Wang, X., Zhang, Q., Lou, Q., Zhang, S., Wang, B., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23094507 · Cited by 26
“Promoter activity plays an important role in the regulation of gene functions [45].”
BackgroundSteenwyk, J. L., Phillips, M. A., Yang, F. J., Date, S. S., Graham, T. R., Berman, J. G., Hittinger, C. T., & Rokas, A. (2022) · Science Advances · doi:10.1126/sciadv.abn0105 · Cited by 23
McMurray, M. A., Stefan, C. J., Wemmer, M., Odorizzi, G., Emr, S. D., & Thorner, J. W. (2011) · Biological Chemistry · doi:10.1515/bc.2011.091 · Cited by 27
“Similarly, Myo1-GFP, unlike native Myo1 expressed in the same manner wfrom a tetracycline-repressible promoter (Mnaimneh et al., 2004) that replaced the endogenous MYO1 promoterx, was unable to support the growth of cdc10D cells (M.A.M. and J.T., unpublished observations).”
Base-CP proteasome can serve as a platform for stepwise lid formation
Yu, Z., Livnat‐Levanon, N., Kleifeld, O., Mansour, W., Nakasone, M. A., Castañeda, C. A., Dixon, E. K., Fushman, D., Reis, N., Pick, E., et al. (2015) · Bioscience Reports · doi:10.1042/bsr20140173 · Cited by 29
Regulation of SESAME-mediated H3T11 phosphorylation by glycolytic enzymes and metabolites
Yu, Q., Tong, C., Luo, M., Xue, X., Mei, Q., Ma, L., Yu, X., Mao, W., Kong, L., Yu, X., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0175576 · Cited by 26
Global study of holistic morphological effectors in the budding yeast Saccharomyces cerevisiae
Suzuki, G., Wang, Y., Kubo, K., Hirata, E., Ohnuki, S., & Ohya, Y. (2018) · BMC Genomics · doi:10.1186/s12864-018-4526-z · Cited by 28
Cooper, S. J., Finney, G. L., Brown, S. L., Nelson, S. K., Hesselberth, J. R., MacCoss, M. J., & Fields, S. (2010) · Genome Research · doi:10.1101/gr.105825.110 · Cited by 26
“We obtained the tet-promoter collection allowing regulation of essential genes by doxycycline from Open Biosystems (YSC1182) (Mnaimneh et al. 2004).”
MethodRoth, K. M., Byam, J., Fang, F., & Butler, J. S. (2009) · RNA · doi:10.1261/rna.709609 · Cited by 25
DEAD-box RNA helicase Dbp4/DDX10 is an enhancer of α-synuclein toxicity and oligomerization
Popova, B., Wang, D., Pätz, C., Akkermann, D., Lázaro, D. F., Gałka, D., Gulko, M. K., Bohnsack, M. T., Möbius, W., Bohnsack, K. E., et al. (2021) · PLoS Genetics · doi:10.1371/journal.pgen.1009407 · Cited by 26
“Approximately 20% of all clones from the collection show smaller colonies even in absence of doxycycline, suggesting that these genes are very sensitive to changes of the promoter activity [31].”
BackgroundInfluentialImura, Y., Molho, M., Chuang, C.-K., & Nagy, P. D. (2015) · Virology · doi:10.1016/j.virol.2015.05.022 · Cited by 25
“…replication in yeast Previously, we have shown based on ubiquitination null mutants of p33 that ubiquitination of p33 replication protein is required for p33 binding to Vps23p ESCRT-I protein, which binds to ubiquitinated membrane proteins (Morita and Sundquist, 2004; Usami et al., 2009).”
BackgroundNakamata, K., Kurita, T., Bhuiyan, M. S. A., Sato, K., Noda, Y., & Yoda, K. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m706486200 · Cited by 25
Hellauer, K., Lesage, G., Sdicu, A., & Turcotte, B. (2005) · Molecular Pharmacology · doi:10.1124/mol.105.012963 · Cited by 25
“To study the involvement of NCP1 in TPZ toxicity in yeast, the NCP1 promoter of a haploid strain was replaced with a doxycyclinerepressible promoter (Mnaimneh et al., 2004).”
BackgroundZheng, F., Cao, Y., Lv, X., Wang, L., Li, C., Zhang, W., Chen, G., & Liu, W. (2016) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-016-8036-0 · Cited by 24
Self-citationFrom beer to breadboards: yeast as a force for biological innovation
Gaikani, H. K., Stolar, M., Kriti, D., Nislow, C., & Giaever, G. N. (2024) · Genome biology · doi:10.1186/s13059-023-03156-9 · Cited by 29
Shcherbik, N., Chernova, T. A., Chernoff, Y. O., & Pestov, D. G. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw566 · Cited by 24
“To better define this effect, we analyzed yeast strains in which CDC48 is placed under the control of a tetracycline-regulatable promoter (PTET-O7-CDC48) (39).”
Analysis of RNA Helicases in P-Bodies and Stress Granules
Hilliker, A. K. (2012) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/b978-0-12-396546-2.00015-2 · Cited by 24
A role for the yeast cell cycle/splicing factor Cdc40 in the G1/S transition
Kaplan, Y., & Kupiec, M. (2006) · Current Genetics · doi:10.1007/s00294-006-0113-y · Cited by 24
Oxidative stress and neurodegeneration: the yeast model system
Breitenbach, M. (2013) · Frontiers in bioscience · doi:10.2741/4171 · Cited by 27
Chance and necessity in chromosomal gene distributions
Hermsen, R., ten Wolde, P. R., & Teichmann, S. A. (2008) · Trends in Genetics · doi:10.1016/j.tig.2008.02.004 · Cited by 24
“Bussemaker to compute, for each neighboring pair of genes, the Pearson’s correlation coefficient of their expression in about 900 experiments (see references [20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38] for the original publications).”
Functional Characterization of Fission Yeast Transcription Factors by Overexpression Analysis
Vachon, L., Wood, J., Kwon, E.-J. G., Laderoute, A., Chatfield‐Reed, K., Karagiannis, J., & Chua, G. (2013) · Genetics · doi:10.1534/genetics.113.150870 · Cited by 24
“Transcription Factor Overexpression 881 The toe2OE strain exhibits a delay in cytokinesis with thickened and misplaced septa, indicating that this transcription factor functions in the proper formation of the division septum for cytokinesis.”
BackgroundInfluentialSelf-citationSato, K., Noda, Y., & Yoda, K. (2007) · Molecular Biology of the Cell · doi:10.1091/mbc.e07-03-0258 · Cited by 24
CRISPR-UnLOCK: Multipurpose Cas9-Based Strategies for Conversion of Yeast Libraries and Strains
Roggenkamp, E., Giersch, R. M., Wedeman, E., Eaton, M., Turnquist, E., Schrock, M. N., Alkotami, L., Jirakittisonthon, T., Schluter-Pascua, S. E., Bayne, G. H., et al. (2017) · Frontiers in Microbiology · doi:10.3389/fmicb.2017.01773 · Cited by 22
“…a suite of useful gene-tagging cassettes for S. cerevisiae with the majority focused on either (i) biochemical epitope tags (Tagwerker et al., 2006; Moqtaderi and Struhl, 2008; Funakoshi and Hochstrasser, 2009) or (ii) fluorescent protein variants (Sheff and Thorn, 2004; Lee et al., 2013; Malcova…”
BackgroundBasharat, Z., Jahanzaib, M., & Rahman, N. (2021) · Infection Genetics and Evolution · doi:10.1016/j.meegid.2021.105004 · Cited by 23
Bayesian Overlapping Subspace Clustering
Fu, Q., & Banerjee, A. (2009) · Proceedings · doi:10.1109/icdm.2009.132 · Cited by 23
“The microarray gene expression dataset we use consists of 4062 genes and 215 experimental conditions [ 14 ].”
MethodTowards combinatorial transcriptional engineering
Mehrotra, R., Renganaath, K., Kanodia, H., Loake, G. J., & Mehrotra, S. (2017) · Biotechnology Advances · doi:10.1016/j.biotechadv.2017.03.006 · Cited by 23
“But practically, they are limited by factors like prohibitive inducer costs, hypersensitivity to inducer concentrations and transcriptional heterogeneity at the single cell level (Alper and Fischer, 2005; Mnaimneh et al., 2004; Siegele and Hu, 1997).”
BackgroundWu, Y., Zhang, S., Gong, X., Yu, Q., Zhang, Y., Luo, M., Zhang, X., Workman, J. L., Yu, X., & Li, S. (2019) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/j.jgg.2019.11.007 · Cited by 22
α-Synuclein Decreases the Abundance of Proteasome Subunits and Alters Ubiquitin Conjugates in Yeast
Popova, B., Gałka, D., Häffner, N., Wang, D., Schmitt, K., Valerius, O., Knop, M., & Braus, G. H. (2021) · Cells · doi:10.3390/cells10092229 · Cited by 24
“Twelve genes encoding subunits of the 26S proteasome were selected among the conditional alleles of essential genes in the Tet-Promoters Hughes collection (yTHC) [71].”
MethodFrom sequence to function: Insights from natural variation in budding yeasts
Nieduszynski, C. A., & Liti, G. (2011) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2011.02.004 · Cited by 22
“A final approach involves inducible gene inactivation either by transcriptional shut-off [34] or conditional protein destabilisation [35,36].”
BackgroundBurugula, B. B., Jerónimo, C., Pathak, R., Jones, J. W., Robert, F., & Govind, C. K. (2014) · Molecular and Cellular Biology · doi:10.1128/mcb.00695-14 · Cited by 22
“We utilized a strain in which SPT6 expression is driven by a tetracycline-titratable promoter (SPT6-tet) (33) and is repressed in the presence of doxycycline (Dox).”
Method
Metadata
- Authors
- Mnaimneh, S., Davierwala, A. P., Haynes, J., Moffat, J., Peng, W.-T., Zhang, W., Yang, X., Pootoolal, J., Chua, G., Lopez, A., Trochesset, M., Morse, D., Krogan, N. J., Hiley, S. L., Li, Z., Morris, Q., Grigull, J., Mitsakakis, N., Roberts, C. J., Greenblatt, J. F., Boone, C., Kaiser, C. A., Andrews, B. J., & Hughes, T. R.
- Affiliations
- University of Toronto (CA)
- Massachusetts Institute of Technology (US)
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Corresponding author
- Hughes, Timothy R
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2004-07
- Volume
- 118
- Issue
- 1
- Pages
- 31-44
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W1974220691
- Cited by
- 604
- References
- 64
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 17 · 2023: 15 · 2022: 22 · 2021: 21 · 2020: 14 · 2019: 17 · 2018: 17 · 2017: 21 · 2016: 23 · 2015: 26 · 2014: 30 · 2013: 28 · 2012: 32
- FWCI
- 14.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 3303 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- essential genes, Saccharomyces cerevisiae, gene function prediction, ribosome biogenesis, protein secretion, mitochondrial protein import, aminoacylation, proteasome, mutant phenotypes
- MeSH terms
- Alleles, Pharmaceutical Preparations, Genes, Fungal, Mitochondria, Models, Genetic, Promoter Regions, Genetic, Protein Processing, Post-Translational, Ribosomal Proteins, RNA, Transfer, Saccharomyces cerevisiae, Transcription, Genetic, Gene Expression Regulation, Fungal, Gene Deletion, Genes, Essential, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Feedback, Physiological, Saccharomyces cerevisiae Proteins
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