title: Active RNA polymerases: mobile or immobile molecular machines?
abstract: It is widely assumed that active RNA polymerases track along their templates to produce a transcript. We test this using chromosome conformation capture and human genes switched on rapidly and synchronously by tumour necrosis factor alpha (TNFalpha); one is 221 kbp SAMD4A, which a polymerase takes more than 1 h to transcribe. Ten minutes after stimulation, the SAMD4A promoter comes together with other TNFalpha-responsive promoters. Subsequently, these contacts are lost as new downstream ones appear; contacts are invariably between sequences being transcribed. Super-resolution microscopy confirms that nascent transcripts (detected by RNA fluorescence in situ hybridization) co-localize at relevant times. Results are consistent with an alternative view of transcription: polymerases fixed in factories reel in their respective templates, so different parts of the templates transiently lie together.
authors.affiliation: Sir William Dunn School of Pathology, Medical Sciences Division, University of Oxford, Oxford, United Kingdom.
authors.forename: Argyris
authors.initials: A
authors.lastname: Papantonis
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Larkin
authors.forename: Youichiro
authors.initials: Y
authors.lastname: Wada
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ohta
authors.forename: Sigeo
authors.initials: S
authors.lastname: Ihara
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kodama
authors.forename: Peter R
authors.initials: PR
authors.lastname: Cook
mesh_terms: D020029:Base Pairing / Q000235:genetics; D002478:Cells, Cultured; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007438:Introns / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D034443:RNA Transport / Q000187:drug effects; D012097:Repressor Proteins / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D012097:Repressor Proteins; C507993:SAMD4A protein, human; D014409:Tumor Necrosis Factor-alpha; D012321:DNA-Directed RNA Polymerases