Evidence map›Paper›PMID 34288498›Full record

ArticleMolecular systems biology2021

TNF stimulation primarily modulates transcriptional burst size of NF-κB-regulated genes.

Victor L Bass, Victor C Wong, M Elise Bullock, Suzanne Gaudet, Kathryn Miller-Jensen

Open access · goldAbstract read
In one paragraph

Article in Molecular systems biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
1.7field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed, 33 citations in OpenAlex.

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  10. Spatial microenvironments tune immune response dynamics in thebioRxiv : the preprint server for biology · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Victor L BassDepartment of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT, USA.ORCID 0000-0003-2850-7949
Victor C WongDepartment of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT, USA.
M Elise BullockDepartment of Biomedical Engineering, Yale University, New Haven, CT, USA.ORCID 0000-0002-7876-4938
Suzanne GaudetDepartment of Cancer Biology and Center for Cancer Systems Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
Kathryn Miller-JensenDepartment of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT, USA.ORCID 0000-0002-7233-0100
Yale University · USHarvard University · US

Funding

PREDOCTORAL TRAINING PROGRAM IN GENETICST32GM007499 · NIGMS · YALE UNIVERSITY · PI CARLSON, JOHN R, REINKE, VALERIE J · 1985 to 2022
$13.9M
Predoctoral Training Program in VirologyT32AI055403 · NIAID · YALE UNIVERSITY · PI KUMAR, PRITI, MOTHES, WALTHER H · 2003 to 2024
$3.6M
Systems analysis of cell-to-cell variability and signaling-transcription factor motifs regulating macrophage responses to conflicting environmental cuesR01GM123011 · NIGMS · YALE UNIVERSITY · PI MILLER-JENSEN, KATHRYN · 2017 to 2025
$2.5M
Convergent Graduate Training in Engineering, Physics and BiologyT32EB019941 · NIBIB · YALE UNIVERSITY · PI O'HERN, COREY · 2016 to 2020
$998k
NIAID NIH HHS T32 AI055403NIBIB NIH HHS T32 EB019941NIGMS NIH HHS R01 GM123011NIGMS NIH HHS T32 GM007499
6 · The paper itself

Abstract

Cell-to-cell heterogeneity is a feature of the tumor necrosis factor (TNF)-stimulated inflammatory response mediated by the transcription factor NF-κB, motivating an exploration of the underlying sources of this noise. Here, we combined single-transcript measurements with computational models to study transcriptional noise at six NF-κB-regulated inflammatory genes. In the basal state, NF-κB-target genes displayed an inverse correlation between mean and noise characteristic of transcriptional bursting. By analyzing transcript distributions with a bursting model, we found that TNF primarily activated transcription by increasing burst size while maintaining burst frequency for gene promoters with relatively high basal histone 3 acetylation (AcH3) that marks open chromatin environments. For promoters with lower basal AcH3 or when AcH3 was decreased with a small molecule drug, the contribution of burst frequency to TNF activation increased. Finally, we used a mathematical model to show that TNF positive feedback amplified gene expression noise resulting from burst size-mediated transcription, leading to a subset of cells with high TNF protein expression. Our results reveal potential sources of noise underlying intercellular heterogeneity in the TNF-mediated inflammatory response.

Indexed as

NF-kappa BTumor Necrosis Factor-alphaAcetylationGene Expression RegulationPromoter Regions, GeneticNF-kappa BTumor Necrosis Factor-alphainflammationNF-κBTNFtranscriptional bursting

Identifiers

PMID34288498
PMCPMC8290835
OpenAlexW3185999759

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.