title: Transcription factors modulate c-Fos transcriptional bursts.
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.
authors: 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.
authors: Adrien
authors: A
authors: Senecal
authors: Department of Chemical and Biological Engineering, Colorado State University, Fort Collins, CO 80523, USA.
authors: Brian
authors: B
authors: Munsky
authors: Functional Imaging of Transcription, Ecole Normale Supérieure, Institut de Biologie de l'ENS (IBENS), and Inserm U1024, and CNRS UMR 8197, Paris 75005, France.
authors: Florence
authors: F
authors: Proux
authors: Functional Imaging of Transcription, Ecole Normale Supérieure, Institut de Biologie de l'ENS (IBENS), and Inserm U1024, and CNRS UMR 8197, Paris 75005, France.
authors: Nathalie
authors: N
authors: Ly
authors: Functional Imaging of Transcription, Ecole Normale Supérieure, Institut de Biologie de l'ENS (IBENS), and Inserm U1024, and CNRS UMR 8197, Paris 75005, France.
authors: Floriane E
authors: FE
authors: Braye
authors: Institut Pasteur, Unité Imagerie et Modélisation, CNRS Unité de Recherche Associée 2582, 75015 Paris, France.
authors: Christophe
authors: C
authors: Zimmer
authors: 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.
authors: Florian
authors: F
authors: Mueller
authors: 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.
authors: Xavier
authors: X
authors: Darzacq
mesh_terms: D000483:Alleles; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D006801:Humans; D008957:Models, Genetic; D017434:Protein Structure, Tertiary; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013269:Stochastic Processes; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D014157:Transcription Factors; D012321:DNA-Directed RNA Polymerases