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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.

Original publication




Journal article


PLoS Biol

Publication Date





Base Pairing, Cells, Cultured, Chromosomes, Human, Pair 14, DNA-Directed RNA Polymerases, Enzyme Activation, Humans, In Situ Hybridization, Fluorescence, Introns, Protein Binding, RNA Transport, Repressor Proteins, Time Factors, Transcription, Genetic, Transcriptional Activation, Tumor Necrosis Factor-alpha