title: Mammalian genes are transcribed with widely different bursting kinetics.
abstract: In prokaryotes and eukaryotes, most genes appear to be transcribed during short periods called transcriptional bursts, interspersed by silent intervals. We describe how such bursts generate gene-specific temporal patterns of messenger RNA (mRNA) synthesis in mammalian cells. To monitor transcription at high temporal resolution, we established various gene trap cell lines and transgenic cell lines expressing a short-lived luciferase protein from an unstable mRNA, and recorded bioluminescence in real time in single cells. Mathematical modeling identified gene-specific on- and off-switching rates in transcriptional activity and mean numbers of mRNAs produced during the bursts. Transcriptional kinetics were markedly altered by cis-regulatory DNA elements. Our analysis demonstrated that bursting kinetics are highly gene-specific, reflecting refractory periods during which genes stay inactive for a certain time before switching on again.
authors.affiliation: Department of Molecular Biology, Sciences III, University of Geneva, 30 Quai Ernest Ansermet, 1211 Geneva, Switzerland.
authors.forename: David M
authors.initials: DM
authors.lastname: Suter
authors.forename: Nacho
authors.initials: N
authors.lastname: Molina
authors.forename: David
authors.initials: D
authors.lastname: Gatfield
authors.forename: Kim
authors.initials: K
authors.lastname: Schneider
authors.forename: Ueli
authors.initials: U
authors.lastname: Schibler
authors.forename: Felix
authors.initials: F
authors.lastname: Naef
mesh_terms: D000107:Acetylation; D000818:Animals; D002478:Cells, Cultured; D002843:Chromatin / Q000502:physiology; D002940:Circadian Rhythm / Q000235:genetics; D015536:Down-Regulation; D015870:Gene Expression; D006657:Histones / Q000378:metabolism; D007700:Kinetics; D008163:Luminescent Measurements; D051379:Mice; D008957:Models, Genetic; D041681:NIH 3T3 Cells; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013269:Stochastic Processes; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D019076:Transgenes; D015854:Up-Regulation
chemical_list: D002843:Chromatin; D006657:Histones; D012333:RNA, Messenger