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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.

Original publication




Journal article



Publication Date





4404 - 4414


Chromosomes, Cytokines, Cytoplasm, DNA-Directed RNA Polymerases, Endothelial Cells, Gene Expression Regulation, Humans, In Situ Hybridization, In Situ Hybridization, Fluorescence, MicroRNAs, N-Acetylglucosaminyltransferases, NF-kappa B, Protein Conformation, Repressor Proteins, Signal Transduction, Smad Proteins, Time Factors, Transcription, Genetic, Transforming Growth Factor beta, Tumor Necrosis Factor-alpha