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

Tumour necrosis factor alpha (TNF alpha) is a potent cytokine that signals through nuclear factor kappa B (NF kappa B) 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 TNF alpha induces responsive genes to congregate in discrete 'N F kappa B 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. The EMBO Journal (2012) 31, 4404-4414. doi:10.1038/emboj.2012.288; Published online 26 October 2012