Mammalian genes are transcribed with widely different bursting kinetics
Open accessAbstract
In prokaryotes and eukaryotes, most genes appear to be transcribed during short periods called transcriptional bursts, interspersed by silent intervals. We describe how such bursts generate gene-specific temporal patterns of messenger RNA (mRNA) synthesis in mammalian cells. To monitor transcription at high temporal resolution, we established various gene trap cell lines and transgenic cell lines expressing a short-lived luciferase protein from an unstable mRNA, and recorded bioluminescence in real time in single cells. Mathematical modeling identified gene-specific on- and off-switching rates in transcriptional activity and mean numbers of mRNAs produced during the bursts. Transcriptional kinetics were markedly altered by cis-regulatory DNA elements. Our analysis demonstrated that bursting kinetics are highly gene-specific, reflecting refractory periods during which genes stay inactive for a certain time before switching on again.
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Promoter state is not solely determined by instantaneous TF occupancy, consistent with a model in which the timescales of TF binding and promoter activation are similar, and suggests that promoters integrate information from multiple rounds of TF binding.
“The finding that promoter state is not solely determined by instantaneous TF occupancy is consistent with a model in which the timescales of TF binding and promoter activation are similar (compare Fig. 3H to Fig. S4K for dissimilar timescales) and suggests that promoters integrate information from multiple rounds of TF binding34,35”
From Single-molecule states link transcription factor binding to gene expression (2024) · cites this paper as [34]
When one takes into account the pulsatile nature of transcription and the stochastic nature of RNA-seq transcript sampling, the observed numbers of neurons expressing NPP genes might be best understood as lower limits.
“When one takes into account the pulsatile nature of transcription (Suter et al., 2011) and the stochastic nature of RNA-seq transcript sampling (Fu and Pachter, 2016; Kim et al., 2015; Tasic et al., 2016), these numbers might be best understood as lower limits.”
From Single-cell transcriptomic evidence for dense intracortical neuropeptide networks (2019) · cites this paper as Suter et al., 2011
The observed numbers of neurons expressing NP-GPCR genes must be understood as lower limits after taking into account pulsatile transcription and stochastic sampling.
“Again, these numbers must be understood as lower limits to percentages of cortical neurons actually expressing at least one of the 29 NP-GPCR genes, after taking into account the pulsatile transcription and stochastic sampling issues cited above.”
From Single-cell transcriptomic evidence for dense intracortical neuropeptide networks (2019) · cites this paper as Suter et al., 2011
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“1, despite qualitatively similar bursty traces from different organisms, bursts unfold across markedly distinct timescales ranging from several minutes [15, 16], to tens of minutes [17, 18], all the way to multiple hours [19].”
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- Authors
- Suter, D. M., Molina, N., Gatfield, D., Schneider, K., Schibler, U., & Naef, F.
- Affiliations
- University of Geneva (CH)
- SIB Swiss Institute of Bioinformatics (CH)
- Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne and Swiss Institute of Bioinformatics, AAB 021 Station 15, CH-1015 Lausanne, Switzerland.
- Venue
- Science
- Published
- 2011-04-22
- Volume
- 332
- Issue
- 6028
- Pages
- 472-474
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2105512180
- Cited by
- 927
- References
- 40
- Citations by year
- 2026: 40 · 2025: 54 · 2024: 69 · 2023: 53 · 2022: 60 · 2021: 76 · 2020: 86 · 2019: 80 · 2018: 65 · 2017: 54 · 2016: 61 · 2015: 57 · 2014: 40 · 2013: 59 · 2012: 59
- FWCI
- 22.35
- Type
- journal article
- Language
- en
- Open access
- green
- infoscience.epfl.ch
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- 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, transcriptional kinetics, mRNA synthesis, refractory period, cis-regulatory elements, luciferase reporter, mammalian gene expression
- MeSH terms
- Acetylation, Animals, Cells, Cultured, Chromatin, Circadian Rhythm, Histones, Kinetics, Luminescent Measurements, Models, Genetic, Promoter Regions, Genetic, RNA, Messenger, Stochastic Processes, Transcription, Genetic, Protein Biosynthesis, Transcriptional Activation, Down-Regulation, Up-Regulation, Gene Expression, Transgenes, NIH 3T3 Cells, Mice
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