Format

Send to

Choose Destination
Cell Rep. 2014 Jul 10;8(1):75-83. doi: 10.1016/j.celrep.2014.05.053. Epub 2014 Jun 26.

Transcription factors modulate c-Fos transcriptional bursts.

Author information

1
Functional Imaging of Transcription, Ecole Normale Supérieure, Institut de Biologie de l'ENS (IBENS), and Inserm U1024, and CNRS UMR 8197, Paris 75005, France; Transcription Imaging Consortium, Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA; UPMC University Paris 06, 75005 Paris, France.
2
Department of Chemical and Biological Engineering, Colorado State University, Fort Collins, CO 80523, USA.
3
Functional Imaging of Transcription, Ecole Normale Supérieure, Institut de Biologie de l'ENS (IBENS), and Inserm U1024, and CNRS UMR 8197, Paris 75005, France.
4
Institut Pasteur, Unité Imagerie et Modélisation, CNRS Unité de Recherche Associée 2582, 75015 Paris, France.
5
Functional Imaging of Transcription, Ecole Normale Supérieure, Institut de Biologie de l'ENS (IBENS), and Inserm U1024, and CNRS UMR 8197, Paris 75005, France; Institut Pasteur, Unité Imagerie et Modélisation, CNRS Unité de Recherche Associée 2582, 75015 Paris, France. Electronic address: florian.muller@pasteur.fr.
6
Functional Imaging of Transcription, Ecole Normale Supérieure, Institut de Biologie de l'ENS (IBENS), and Inserm U1024, and CNRS UMR 8197, Paris 75005, France; Transcription Imaging Consortium, Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA. Electronic address: darzacq@berkeley.edu.

Abstract

Transcription is a stochastic process occurring mostly in episodic bursts. Although the local chromatin environment is known to influence the bursting behavior on long timescales, the impact of transcription factors (TFs)--especially in rapidly inducible systems--is largely unknown. Using fluorescence in situ hybridization and computational models, we quantified the transcriptional activity of the proto-oncogene c-Fos with single mRNA accuracy at individual endogenous alleles. We showed that, during MAPK induction, the TF concentration modulates the burst frequency of c-Fos, whereas other bursting parameters remain mostly unchanged. By using synthetic TFs with TALE DNA-binding domains, we systematically altered different aspects of these bursts. Specifically, we linked the polymerase initiation frequency to the strength of the transactivation domain and the burst duration to the TF lifetime on the promoter. Our results show how TFs and promoter binding domains collectively act to regulate different bursting parameters, offering a vast, evolutionarily tunable regulatory range for individual genes.

PMID:
24981864
PMCID:
PMC5555219
DOI:
10.1016/j.celrep.2014.05.053
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center