Transcription Factors Modulate c-Fos Transcriptional Bursts

Adrien Senecal (1, 2, 3) , Brian Munsky (4) , Florence Proux (1) , Nathalie Ly (1) , Floriane E. Braye (1) , Christophe Zimmer (5) , Florian Mueller (1, 5) , Xavier Darzacq (1, 2)

1 IBENS - Institut de biologie de l'ENS Paris
2 HHMI - Howard Hughes Medical Institute
3 UPMC - Université Pierre et Marie Curie - Paris 6
4 CSU - Colorado State University [Fort Collins]
5 Imagerie et Modélisation

Transcription is a stochastic process occurring mostly in episodic bursts. Although the local chro-matin 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.

Domaines: Biologie cellulaire

Adrien Senecal, Brian Munsky, Florence Proux, Nathalie Ly, Floriane E. Braye, et al.. Transcription Factors Modulate c-Fos Transcriptional Bursts. Cell Reports, 2014, 8 (1), pp.75-83. ⟨10.1016/j.celrep.2014.05.053⟩. ⟨hal-01312884⟩