title: Space exploration by the promoter of a long human gene during one transcription cycle.
abstract: An RNA polymerase has been thought to transcribe by seeking out a promoter, initiating and then tracking down the template. We add tumor necrosis factor α to primary human cells, switch on transcription of a 221-kb gene and monitor promoter position during the ensuing transcription cycle (using RNA fluorescence in situ hybridization coupled to super-resolution localization, chromosome conformation capture and Monte Carlo simulations). Results are consistent with a polymerase immobilized in a 'factory' capturing a promoter and reeling in the template, as the transcript and promoter are extruded. Initially, the extruded promoter is tethered close to the factory and so likely to re-initiate; later, the tether becomes long enough to allow re-initiation in another factory. We suggest close tethering underlies enhancer function and transcriptional 'bursting'.
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Larkin
authors.forename: Argyris
authors.initials: A
authors.lastname: Papantonis
authors.forename: Peter R
authors.initials: PR
authors.lastname: Cook
authors.forename: Davide
authors.initials: D
authors.lastname: Marenduzzo
mesh_terms: D002478:Cells, Cultured; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008957:Models, Genetic; D009010:Monte Carlo Method; D011401:Promoter Regions, Genetic; D012313:RNA / Q000032:analysis; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics; D013698:Templates, Genetic; D014158:Transcription, Genetic
chemical_list: D012097:Repressor Proteins; C507993:SAMD4A protein, human; D012313:RNA; D012321:DNA-Directed RNA Polymerases