First Responders Shape a Prompt and Sharp NF-κB-Mediated Transcriptional Response to TNF-α - Archive ouverte HAL Access content directly
Journal Articles iScience Year : 2020

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

Samuel Zambrano
  • Function : Author
Alessia Loffreda
  • Function : Author
Elena Carelli
  • Function : Author
Giacomo Stefanelli
  • Function : Author
Federica Colombo
  • Function : Author
Carlo Tacchetti
  • Function : Author
Alessandra Agresti
  • Function : Author
Marco Bianchi
  • Function : Author
Davide Mazza
  • Function : Correspondent author
  • PersonId : 1084783

Connectez-vous pour contacter l'auteur

Abstract

NF-kB 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 transcription of NF-kB target genes is heterogeneous in individual cells but yet results in an average nascent transcription profile that is prompt (i.e. occurs almost immediately) and sharp (i.e. increases and decreases rapidly) compared to NF-B nuclear localization. Using an NF-kB-controlled MS2 reporter we show that the single-cell nascent transcription is more heterogeneous than NF-kB translocation dynamics, with a fraction of synchronized "first responders" that shape the average transcriptional profile and are more prone to respond to multiple TNF-a stimulations. A mathematical model combining NF-kB 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.
Fichier principal
Vignette du fichier
Zambrano_et_al_2020.pdf (11.19 Mo) Télécharger le fichier
Origin : Files produced by the author(s)

Dates and versions

hal-03044483 , version 1 (09-12-2020)

Identifiers

Cite

Samuel Zambrano, Alessia Loffreda, Elena Carelli, Giacomo Stefanelli, Federica Colombo, et al.. First Responders Shape a Prompt and Sharp NF-κB-Mediated Transcriptional Response to TNF-α. iScience, 2020, 23 (9), pp.101529. ⟨10.1016/j.isci.2020.101529⟩. ⟨hal-03044483⟩
56 View
11 Download

Altmetric

Share

Gmail Facebook X LinkedIn More