Evidence map›Paper›PMID 33083759›Full record

ArticleiScience2020

First Responders Shape a Prompt and Sharp NF-κB-Mediated Transcriptional Response to TNF-α.

Samuel Zambrano, Alessia Loffreda, Elena Carelli, Giacomo Stefanelli, Federica Colombo, Edouard Bertrand, Carlo Tacchetti, Alessandra Agresti, Marco E Bianchi, Nacho Molina and 1 more

Abstract read
In one paragraph

Article in iScience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
–field-weighted citation impact
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

12 citing papers in PubMed.

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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

11 authors.

Samuel ZambranoSchool of Medicine, Vita-Salute San Raffaele University, Milan 20132, Italy.
Alessia LoffredaExperimental Imaging Center, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy.
Elena CarelliDivision of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy.
Giacomo StefanelliExperimental Imaging Center, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy.
Federica ColomboDivision of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy.
Edouard BertrandInstitut de Génétique Moléculaire de Montpellier, CNRS, Montpellier 34293, France.
Carlo TacchettiSchool of Medicine, Vita-Salute San Raffaele University, Milan 20132, Italy.
Alessandra AgrestiDivision of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy.
Marco E BianchiSchool of Medicine, Vita-Salute San Raffaele University, Milan 20132, Italy.
Nacho MolinaInstitut de Génétique et Biologie Moléculaire Cellulaire, Illkirch-Graffenstaden 67404, France.
Davide MazzaExperimental Imaging Center, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Nuclear factor (NF)-κB controls the transcriptional response to inflammatory signals by translocating into the nucleus, but we lack a single-cell characterization of the resulting transcription dynamics. Here we show that upon tumor necrosis factor (TNF)-α transcription of NF-κB target genes is heterogeneous in individual cells but results in an average nascent transcription profile that is prompt (i.e., occurs almost immediately) and sharp (i.e., increases and decreases rapidly) compared with NF-κB nuclear localization. Using an NF-κB-controlled MS2 reporter we show that the single-cell nascent transcription is more heterogeneous than NF-κB translocation dynamics, with a fraction of synchronized "first responders" that shape the average transcriptional profile and are more prone to respond to multiple TNF-α stimulations. A mathematical model combining NF-κB-mediated gene activation and a gene refractory state is able to reproduce these features. Our work shows how the expression of target genes induced by transcriptional activators can be heterogeneous across single cells and yet time resolved on average.

Indexed as

Biological SciencesBiophysicsImmunologyMolecular BiologySystems Biology

Identifiers

PMID33083759
PMCPMC7509218

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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.