TNFα signals through specialized factories where responsive coding and miRNA genes are transcribed

• DOI: 10.1038/emboj.2012.288
• Publication Date: 2012-10-26T14:14:47Z
• Authors: Argyris Papantonis; Takahide Kohro; Sabyasachi Baboo; Joshua D Larkin; Binwei Deng; Patrick Short; Shuichi Tsutsumi; Stephen Taylor; Yasuharu Kanki; Mika Kobayashi; Guoliang Li; Huay-Mei Poh; Xiaoan Ruan; Hiroyuki Aburatani; Yijun Ruan; Tatsuhiko Kodama; Youichiro Wada; Peter R Cook
• Keywords: 0301 basic medicine; Cytoplasm; Time Factors; Transcription, Genetic; Protein Conformation; Tumor Necrosis Factor-alpha; NF-kappa B; Endothelial Cells; Smad Proteins; DNA-Directed RNA Polymerases; N-Acetylglucosaminyltransferases; Chromosomes; Repressor Proteins; MicroRNAs; 03 medical and health sciences; Gene Expression Regulation; Transforming Growth Factor beta; Cytokines; Humans; In Situ Hybridization; In Situ Hybridization, Fluorescence; Signal Transduction

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.