The DOI matches its Crossref record; 61 of the 63 references it cites were found in a registry or an index.
Single-RNA counting reveals alternative modes of gene expression in yeast
Open accessAbstract
Proper execution of transcriptional programs is a key requirement of gene expression regulation, demanding accurate control of timing and amplitude. How precisely the transcription machinery fulfills this task is not known. Using an in situ hybridization approach that detects single mRNA molecules, we measured mRNA abundance and transcriptional activity within single Saccharomyces cerevisiae cells. We found that expression levels for particular genes are higher than initially reported and can vary substantially among cells. However, variability for most constitutively expressed genes is unexpectedly small. Combining single-transcript measurements with computational modeling indicates that low expression variation is achieved by transcribing genes using single transcription-initiation events that are clearly separated in time, rather than by transcriptional bursts. In contrast, PDR5, a gene regulated by the transcription coactivator complex SAGA, is expressed using transcription bursts, resulting in larger variation. These data directly demonstrate the existence of multiple expression modes used to modulate the transcriptome.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“In recent years, single-molecule fluorescence microscopy has been used to count mRNA (12-16) or protein (8, 17) molecules in individual cells, especially in bacteria. However, these methods have only been applied to limited number of specific genes.”
From Quantifying E. coli Proteome and Transcriptome with Single-Molecule Sensitivity in Single Cells (2010) · cites this paper as [16]
In the citing paper
“SCM estimates of absolute mRNA levels matched FISH measurements well [53] (average difference of 1.2-fold between estimated and measured levels [Fig 5B], with one outlier estimate overshooting the FISH value by 1.7-fold).”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Stochastic Gene Expression in a Single Cell
Elowitz, M. B., Levine, A. J., Siggia, E. D., & Swain, P. S. (2002) · Science · doi:10.1126/science.1070919 · Cited by 5,441
Spellman, P. T., Sherlock, G. J., Zhang, M. Q., Iyer, V. R., Anders, K. R., Eisen, M. B., Brown, P. O., Botstein, D., & Futcher, B. (1998) · Molecular Biology of the Cell · doi:10.1091/mbc.9.12.3273 · Cited by 4,724
Global analysis of protein expression in yeast
Ghaemmaghami, S., Huh, W.-K., Bower, K., Howson, R. W., Belle, A., Dephoure, N., O'Shea, E. K., & Weissman, J. S. (2003) · Nature · doi:10.1038/nature02046 · Cited by 3,750
The Role of Chromatin during Transcription
Li, B., Carey, M., & Workman, J. L. (2007) · Cell · doi:10.1016/j.cell.2007.01.015 · Cited by 3,503
Precise Nanometer Localization Analysis for Individual Fluorescent Probes
Thompson, R. E., Larson, D. R., & Webb, W. W. (2002) · Biophysical Journal · doi:10.1016/s0006-3495(02)75618-x · Cited by 2,320
Self-citationStochasticity in gene expression: from theories to phenotypes
Kærn, M., Elston, T. C., Blake, W. J., & Collins, J. J. (2005) · Nature Reviews Genetics · doi:10.1038/nrg1615 · Cited by 2,318
Transcriptional regulatory code of a eukaryotic genome
Harbison, C. T., Gordon, D. B., Lee, T. I., Rinaldi, N. J., MacIsaac, K. D., Danford, T., Hannett, N. M., Tagne, J., Reynolds, D. B., Yoo, J. Y., et al. (2004) · Nature · doi:10.1038/nature02800 · Cited by 2,135
The economics of ribosome biosynthesis in yeast
Warner, J. R. (1999) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(99)01460-7 · Cited by 1,933
Stochastic mRNA Synthesis in Mammalian Cells
Raj, A., Peskin, C. S., Tranchina, D., Vargas, D. Y., & Tyagi, S. (2006) · PLoS Biology · doi:10.1371/journal.pbio.0040309 · Cited by 1,737
Dissecting the regulatory circuitry of a eukaryotic genome
Holstege, F. C. P., Jennings, E. G., Wyrick, J. J., Lee, T. I., Hengartner, C. J., Green, M. R., Golub, T. R., Lander, E. S., & Young, R. A. (1998) · Cell · doi:10.1016/s0092-8674(00)81641-4 · Cited by 1,670
Visualization of Single RNA Transcripts in Situ
Femino, A. M., Fay, F. S., Fogarty, K., & Singer, R. H. (1998) · Science · doi:10.1126/science.280.5363.585 · Cited by 1,504
Self-citationA genomic code for nucleosome positioning
Segal, E., Fondufe‐Mittendorf, Y. N., Chen, L., Thåström, A., Field, Y., Moore, I. K., Wang, J.-P. Z., & Widom, J. (2006) · Nature · doi:10.1038/nature04979 · Cited by 1,492
Single-cell proteomic analysis of S. cerevisiae reveals the architecture of biological noise
Newman, J. R. S., Ghaemmaghami, S., Ihmels, J., Breslow, D. K., Noble, M., DeRisi, J. L., & Weissman, J. S. (2006) · Nature · doi:10.1038/nature04785 · Cited by 1,483
Real-Time Kinetics of Gene Activity in Individual Bacteria
Golding, I., Paulsson, J., Zawilski, S. M., & Cox, E. C. (2005) · Cell · doi:10.1016/j.cell.2005.09.031 · Cited by 1,468
Control of Stochasticity in Eukaryotic Gene Expression
Raser, J. M., & O'Shea, E. K. (2004) · Science · doi:10.1126/science.1098641 · Cited by 1,425
The General Transcription Machinery and General Cofactors
Thomas, M. C., & Chiang, C. (2006) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409230600648736 · Cited by 992
Genome-wide expression monitoring in Saccharomyces cerevisiae
Wodicka, L. M., Dong, H., Mittmann, M., Ho, M.-H., & Lockhart, D. J. (1997) · Nature Biotechnology · doi:10.1038/nbt1297-1359 · Cited by 973
Characterization of the Yeast Transcriptome
Velculescu, V. E., Zhang, L., Zhou, W., Vogelstein, R. J., Basrai, M. A., Bassett, D. E., Hieter, P., Vogelstein, B., & Kinzler, K. W. (1997) · Cell · doi:10.1016/s0092-8674(00)81845-0 · Cited by 973
Probing Gene Expression in Live Cells, One Protein Molecule at a Time
Yu, J., Xiao, J., Ren, X., Lao, K., & Xie, X. S. (2006) · Science · doi:10.1126/science.1119623 · Cited by 918
A Unified Theory of Gene Expression
Orphanides, G., & Reinberg, D. (2002) · Cell · doi:10.1016/s0092-8674(02)00655-4 · Cited by 898
The glucocorticoid receptor: rapid exchange with regulatory sites in living cells
McNally, J. G., Müller, W. G., Walker, D., Wolford, R., & Hager, G. L. (2000) · Science · doi:10.1126/science.287.5456.1262 · Cited by 802
Analysis of human transcriptomes
Velculescu, V. E., Madden, S. L., Zhang, L., Lash, A., Yu, J., Rago, C., Lal, A., Wang, C. J., Beaudry, G. A., Ciriello, K. M., et al. (1999) · Nature Genetics · doi:10.1038/70487 · Cited by 775
Transcriptional Pulsing of a Developmental Gene
Chubb, J. R., Trcek, T., Shenoy, S. M., & Singer, R. H. (2006) · Current Biology · doi:10.1016/j.cub.2006.03.092 · Cited by 714
Self-citationPrecision and functional specificity in mRNA decay
Wang, Y., Liu, C. L., Storey, J. D., Tibshirani, R. J., Herschlag, D., & Brown, P. O. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.092538799 · Cited by 714
Quantification of protein half-lives in the budding yeast proteome
Belle, A., Tanay, A., Bitincka, L., Shamir, R., & O’Shea, E. K. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0605420103 · Cited by 678
In vivo dynamics of RNA polymerase II transcription
Darzacq, X., Shav-Tal, Y., de Turris, V., Brody, Y., Shenoy, S. M., Phair, R. D., & Singer, R. H. (2007) · Nature Structural & Molecular Biology · doi:10.1038/nsmb1280 · Cited by 665
Self-citationGenome-wide analysis of mRNA translation profiles in Saccharomyces cerevisiae
Arava, Y., Wang, Y., Storey, J. D., Liu, C. L., Brown, P. O., & Herschlag, D. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0635171100 · Cited by 663
Markovian Modeling of Gene-Product Synthesis
Peccoud, J., & Ycart, B. (1995) · Theoretical Population Biology · doi:10.1006/tpbi.1995.1027 · Cited by 640
Phenotypic Consequences of Promoter-Mediated Transcriptional Noise
Blake, W. J., Balázsi, G., Kohanski, M. A., Isaacs, F. J., Murphy, K. F., Kuang, Y., Cantor, C. R., Walt, D. R., & Collins, J. J. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.11.003 · Cited by 617
Casolari, J. M., Brown, C. R., Komili, S., West, J. A., Hieronymus, H., & Silver, P. A. (2004) · Cell · doi:10.1016/s0092-8674(04)00448-9 · Cited by 604
Huisinga, K. L., & Pugh, B. F. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00087-5 · Cited by 561
Single-Cell Gene Expression Profiling
Levsky, J. M., Shenoy, S. M., Pezo, R. C., & Singer, R. H. (2002) · Science · doi:10.1126/science.1072241 · Cited by 526
Self-citationBreaking barriers to transcription elongation
Saunders, A., Core, L. J., & Lis, J. T. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1981 · Cited by 525
The nuclear envelope and transcriptional control
Akhtar, A., & Gasser, S. M. (2007) · Nature Reviews Genetics · doi:10.1038/nrg2122 · Cited by 457
A transcription reinitiation intermediate that is stabilized by activator
Yudkovsky, N., Ranish, J. A., & Hahn, S. (2000) · Nature · doi:10.1038/35041603 · Cited by 421
Effects of Molecular Memory and Bursting on Fluctuations in Gene Expression
Pedraza, J. M., & Paulsson, J. (2008) · Science · doi:10.1126/science.1144331 · Cited by 404
Distinction and Relationship between Elongation Rate and Processivity of RNA Polymerase II In Vivo
Mason, P. B., & Struhl, K. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.02.017 · Cited by 359
A bottom-up approach to gene regulation
Guido, N. J., Wang, X., Adalsteinsson, D., McMillen, D. R., Hasty, J., Cantor, C. R., Elston, T. C., & Collins, J. J. (2006) · Nature · doi:10.1038/nature04473 · Cited by 327
Nucleosome displacement in transcription: Figure 1.Preprint
Workman, J. L. (2006) · Genes & Development · doi:10.1101/gad.1435706 · Cited by 320
Recycling of the general transcription factors during RNA polymerase II transcription.Preprint
Zawel, L. S., Kumar, K. P., & Reinberg, D. (1995) · Genes & Development · doi:10.1101/gad.9.12.1479 · Cited by 320
Identification of a 60S Preribosomal Particle that Is Closely Linked to Nuclear Export
Baßler, J., Grandi, P., Gadal, O., Leßmann, T., Petfalski, E., Tollervey, D. W., Lechner, J., & Hurt, E. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00342-2 · Cited by 298
Number and distribution of polyadenylated RNA sequences in yeast
Hereford, L. M., & Rosbash, M. (1977) · Cell · doi:10.1016/0092-8674(77)90032-0 · Cited by 261
Edwards, A. M., Kane, C. M., Young, R. A., & Kornberg, R. D. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)52403-0 · Cited by 240
Chen, W., & Struhl, K. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.8.2691 · Cited by 237
Cooperation Between RNA Polymerase Molecules in Transcription Elongation
Epshtein, V., & Nudler, E. (2003) · Science · doi:10.1126/science.1083219 · Cited by 234
Transcription occurs in pulses in muscle fibersPreprint
Newlands, S., Levitt, L. K., Robinson, C. S., Karpf, A. B. C., Hodgson, V. R. M., Wade, R., & Hardeman, E. C. (1998) · Genes & Development · doi:10.1101/gad.12.17.2748 · Cited by 195
The transcriptional cycle of HIV-1 in real-time and live cells
Boireau, S., Maiuri, P., Basyuk, E., de la Mata, M., Knezevich, A., Pradet-Balade, B., Bäcker, V., Kornblihtt, A., Marcello, A., & Bertrand, E. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200706018 · Cited by 191
Ucker, D. S., & Yamamoto, K. R. (1984) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)42806-7 · Cited by 190
Struhl, K. (1986) · Molecular and Cellular Biology · doi:10.1128/mcb.6.11.3847 · Cited by 179
Evidence for distinct mechanisms facilitating transcript elongation through chromatin in vivo
Kristjuhan, A., & Svejstrup, J. Q. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600433 · Cited by 173
Absolute mRNA levels and transcriptional initiation rates in Saccharomyces cerevisiae.
Iyer, V., & Struhl, K. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.11.5208 · Cited by 166
Rapid Changes in Drosophila Transcription After an Instantaneous Heat Shock
O’Brien, T., & Lis, J. T. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.6.3456 · Cited by 163
Chromatin Structure and RNA Polymerase II Connection: Implications for Transcription
Struhl, K. (1996) · Cell · doi:10.1016/s0092-8674(00)80970-8 · Cited by 160
Stochastic gene expression: from single molecules to the proteome
Kaufmann-Malaga, B., & van Oudenaarden, A. (2007) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2007.02.007 · Cited by 159
Transcription of individual genes in eukaryotic cells occurs randomly and infrequently
Ross, I. L., Browne, C. M., & Hume, D. A. (1994) · Immunology and Cell Biology · doi:10.1038/icb.1994.26 · Cited by 140
Concurrent Fast and Slow Cycling of a Transcriptional Activator at an Endogenous Promoter
Karpova, T., Kim, M. J., Spriet, C., Nalley, K., Stasevich, T. J., Kherrouche, Z., Héliot, L., & McNally, J. G. (2008) · Science · doi:10.1126/science.1150559 · Cited by 136
Detours and shortcuts to transcription reinitiation
Dieci, G., & Sentenac, A. (2003) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(03)00054-9 · Cited by 83
Mechanism of Differential Utilization of the his3 T R and T C TATA Elements
Iyer, V. R., & Struhl, K. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.12.7059 · Cited by 76
Transcription Reinitiation Rate: a Special Role for the TATA Box
Yean, D., & Gralla, J. D. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.7.3809 · Cited by 74
Many expressed genes in bacteria and yeast are transcribed only once per cell cycle
Bon, M., McGowan, S. J., & Cook, P. R. (2006) · The FASEB Journal · doi:10.1096/fj.06-6087fje · Cited by 44
The Dynamic Range of Transcription
Darzacq, X., & Singer, R. H. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.05.009 · Cited by 13
Self-citation
Flagged first, then by citations
2 of the 63 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Quantifying E. coli Proteome and Transcriptome with Single-Molecule Sensitivity in Single Cells
Taniguchi, Y., Choi, P. J., Li, G.-W., Chen, H., Babu, M., Hearn, J., Emili, A., & Xie, X. S. (2010) · Science · doi:10.1126/science.1188308 · Cited by 1,982
Functional roles for noise in genetic circuits
Eldar, A., & Elowitz, M. B. (2010) · Nature · doi:10.1038/nature09326 · Cited by 1,482
Mammalian genes are transcribed with widely different bursting kinetics
Suter, D. M., Molina, N., Gatfield, D., Schneider, K., Schibler, U., & Naef, F. (2011) · Science · doi:10.1126/science.1198817 · Cited by 927
Using Gene Expression Noise to Understand Gene Regulation
Munsky, B., Neuert, G., & van Oudenaarden, A. (2012) · Science · doi:10.1126/science.1216379 · Cited by 745
Real-Time Observation of Transcription Initiation and Elongation on an Endogenous Yeast Gene
Larson, D. R., Zenklusen, D., Wu, B., Chao, J. A., & Singer, R. H. (2011) · Science · doi:10.1126/science.1202142 · Cited by 680
Self-citation
Metadata
- Authors
- Zenklusen, D., Larson, D. R., & Singer, R. H.
- Affiliations
- Albert Einstein College of Medicine (US)
- Corresponding author
- Singer, Robert H
- Venue
- Nature Structural & Molecular Biology
- Published
- 2008-11-16
- Volume
- 15
- Issue
- 12
- Pages
- 1263-1271
- ISSN
- 1545-9985 (ISSN-L)
- 1545-9993
- PMC
- PMC3154325
- OpenAlex
- W1992927069
- Cited by
- 684
- References
- 63
- Citations by year
- 2026: 16 · 2025: 25 · 2024: 45 · 2023: 35 · 2022: 22 · 2021: 38 · 2020: 37 · 2019: 40 · 2018: 44 · 2017: 36 · 2016: 52 · 2015: 47 · 2014: 38 · 2013: 64 · 2012: 40
- FWCI
- 14.41
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Structural & Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM057071)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- transcriptional bursting, gene expression variation, Saccharomyces cerevisiae, PDR5, nascent RNA, mRNA levels, housekeeping genes, transcriptional regulation
- MeSH terms
- RNA, Fungal, RNA, Messenger, Saccharomyces cerevisiae, Transcription, Genetic, Trans-Activators, Gene Expression, In Situ Hybridization, Fluorescence, Saccharomyces cerevisiae Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
