@article {45031,
	title = {Transcription factors modulate c-Fos transcriptional bursts.},
	journal = {Cell Reports},
	volume = {8},
	year = {2014},
	month = {2014 Jul 10},
	pages = {75-83},
	abstract = {<p>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\&nbsp;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.</p>
},
	issn = {2211-1247},
	doi = {10.1016/j.celrep.2014.05.053},
	author = {Senecal, Adrien and Munsky, Brian and Proux, Florence and Ly, Nathalie and Braye, Floriane E and Zimmer, Christophe and Mueller, Florian and Darzacq, Xavier}
}
@article {6594,
	title = {Real-time dynamics of RNA polymerase II clustering in live human cells.},
	journal = {Science},
	volume = {341},
	year = {2013},
	month = {2013 Aug 9},
	pages = {664-7},
	abstract = {<p>Transcription is reported to be spatially compartmentalized in nuclear transcription factories with clusters of RNA polymerase II (Pol II). However, little is known about when these foci assemble or their relative stability. We developed a quantitative single-cell approach to characterize protein spatiotemporal organization, with single-molecule sensitivity in live eukaryotic cells. We observed that Pol II clusters form transiently, with an average lifetime of 5.1 ({\textpm} 0.4) seconds, which refutes the notion that they are statically assembled substructures. Stimuli affecting transcription yielded orders-of-magnitude changes in the dynamics of Pol II clusters, which implies that clustering is regulated and plays a role in the cell{\textquoteright}s ability to effect rapid response to external signals. Our results suggest that transient crowding of enzymes may aid in rate-limiting steps of gene regulation.</p>
},
	keywords = {Cell Line, Flavonoids, Gene Expression Regulation, Genetic, Humans, Piperidines, RNA Polymerase II, Single-Cell Analysis, Time Factors, Transcription, Transcription Elongation, Tumor},
	issn = {1095-9203},
	doi = {10.1126/science.1239053},
	author = {Cisse, Ibrahim I and Izeddin, Ignacio and Causse, Sebastien Z and Boudarene, Lydia and Senecal, Adrien and Muresan, Leila and Dugast-Darzacq, Claire and Hajj, Bassam and Dahan, Maxime and Darzacq, Xavier}
}
