title: TNFα signals through specialized factories where responsive coding and miRNA genes are transcribed.
abstract: Tumour necrosis factor alpha (TNFα) is a potent cytokine that signals through nuclear factor kappa B (NFκB) to activate a subset of human genes. It is usually assumed that this involves RNA polymerases transcribing responsive genes wherever they might be in the nucleus. Using primary human endothelial cells, variants of chromosome conformation capture (including 4C and chromatin interaction analysis with paired-end tag sequencing), and fluorescence in situ hybridization to detect single nascent transcripts, we show that TNFα induces responsive genes to congregate in discrete 'NFκB factories'. Some factories further specialize in transcribing responsive genes encoding micro-RNAs that target downregulated mRNAs. We expect all signalling pathways to contain this extra leg, where responding genes are transcribed in analogous specialized factories.
authors.affiliation: The Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
authors.forename: Argyris
authors.initials: A
authors.lastname: Papantonis
authors.forename: Takahide
authors.initials: T
authors.lastname: Kohro
authors.forename: Sabyasachi
authors.initials: S
authors.lastname: Baboo
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Larkin
authors.forename: Binwei
authors.initials: B
authors.lastname: Deng
authors.forename: Patrick
authors.initials: P
authors.lastname: Short
authors.forename: Shuichi
authors.initials: S
authors.lastname: Tsutsumi
authors.forename: Stephen
authors.initials: S
authors.lastname: Taylor
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Kanki
authors.forename: Mika
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Guoliang
authors.initials: G
authors.lastname: Li
authors.forename: Huay-Mei
authors.initials: HM
authors.lastname: Poh
authors.forename: Xiaoan
authors.initials: X
authors.lastname: Ruan
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aburatani
authors.forename: Yijun
authors.initials: Y
authors.lastname: Ruan
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kodama
authors.forename: Youichiro
authors.initials: Y
authors.lastname: Wada
authors.forename: Peter R
authors.initials: PR
authors.lastname: Cook
mesh_terms: D002875:Chromosomes / Q000648:ultrastructure; D016207:Cytokines / Q000096:biosynthesis; D003593:Cytoplasm / Q000378:metabolism; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology; D005786:Gene Expression Regulation; D006801:Humans; D017403:In Situ Hybridization; D017404:In Situ Hybridization, Fluorescence; D035683:MicroRNAs / Q000378:metabolism*; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011487:Protein Conformation; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D000099058:Exostosin 1
chemical_list: D016207:Cytokines; D035683:MicroRNAs; D016328:NF-kappa B; D012097:Repressor Proteins; C507993:SAMD4A protein, human; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D017351:N-Acetylglucosaminyltransferases; D000099058:Exostosin 1; D012321:DNA-Directed RNA Polymerases