Enhancer Regulation of Transcriptional Bursting Parameters Revealed by Forced Chromatin Looping
Open accessAbstract
Mammalian genes transcribe RNA not continuously, but in bursts. Transcriptional output can be modulated by altering burst fraction or burst size, but how regulatory elements control bursting parameters remains unclear. Single-molecule RNA FISH experiments revealed that the β-globin enhancer (LCR) predominantly augments transcriptional burst fraction of the β-globin gene with modest stimulation of burst size. To specifically measure the impact of long-range chromatin contacts on transcriptional bursting, we forced an LCR-β-globin promoter chromatin loop. We observed that raising contact frequencies increases burst fraction but not burst size. In cells in which two developmentally distinct LCR-regulated globin genes are cotranscribed in cis, burst sizes of both genes are comparable. However, allelic co-transcription of both genes is statistically disfavored, suggesting mutually exclusive LCR-gene contacts. These results are consistent with competition between the β-type globin genes for LCR contacts and suggest that LCR-promoter loops are formed and released with rapid kinetics.
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Enhancers increase the frequency of transcriptional bursts without significantly affecting their amplitude and duration.
“Evidence from live imaging and single-cell transcriptomics indicates that enhancers increase the frequency of transcriptional bursts without significantly affecting their amplitude and duration [310, 505, 516].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [505]
The Results section reports that forced LCR–promoter contacts increased β-globin burst fraction without changing burst size, supporting the frequency and amplitude portions for that intervention. But enhancer deletion had a lesser yet significant effect on burst size, and the Discussion says burst duration could not be determined definitively. The paper therefore does not support the unqualified claim that enhancers leave amplitude and duration unaffected. (LLM, conf=0.88)
Experimental — accuracy not yet measuredEnhancers increase the frequency of transcription cycles, while their duration is determined by the properties of the promoter.
“Existing experimental data suggest that enhancers increase the frequency of cycles, while their duration is determined by the properties of the promoter [53,54,55,56].”
From Enhancer Function in the 3D Genome (2023) · cites this paper as [54]
The Results report that forced enhancer–promoter contacts increased β-globin burst fraction, a measure related to burst frequency, without changing burst size. The Discussion says burst duration could not be determined definitively; it does not establish that promoter properties determine duration. The finding also concerns the β-globin locus rather than enhancers generally. (LLM, conf=0.89)
Experimental — accuracy not yet measuredIn the β-globin locus, interactions between the LCR and the γ-globin or the β-globin genes can switch very rapidly on the same DNA strand.
“in the β-globin locus, interactions between the LCR and the γ-globin or the β-globin genes can switch very rapidly on the same DNA strand [505].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [505]
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- Authors
- Bartman, C. R., Hsu, S. C., Hsiung, C. C.-S., Raj, A., & Blobel, G. A.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Raj, Arjun
- Blobel, Gerd A.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2016-04
- Volume
- 62
- Issue
- 2
- Pages
- 237-247
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC4842148
- OpenAlex
- W2315188941
- Cited by
- 345
- References
- 12
- Citations by year
- 2026: 13 · 2025: 32 · 2024: 32 · 2023: 34 · 2022: 27 · 2021: 61 · 2020: 40 · 2019: 36 · 2018: 38 · 2017: 21 · 2016: 11
- FWCI
- 18.37
- 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, 385 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
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Science Foundation (1350601, 1RO1 HL119479, 1U01HL129998)
- National Institutes of Health (1DP2OD008514, R33 1R33EB019767)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- transcriptional bursting, enhancer-promoter looping, long-range chromatin contacts, beta-globin locus control region, burst size, cis-regulation, single-molecule RNA FISH, globin gene regulation
- MeSH terms
- Animals, Cell Line, Chromatin, Enhancer Elements, Genetic, Erythroblasts, Erythropoiesis, Humans, Kinetics, Promoter Regions, Genetic, RNA, Messenger, Transcription, Genetic, Transfection, Transcriptional Activation, In Situ Hybridization, Fluorescence, Locus Control Region, Chromatin Assembly and Disassembly, Mice, beta-Globins, Primary Cell Culture
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