Specialized factories mediate the transcriptional response to TNF-alpha signaling

Tumor necrosis factor alpha (TNF-alpha) is a potent cytokine that signals through nuclear factor-kappa B (NFkappaB) to activate a subset of human genes. It is usually assumed this involves RNA polymerases transcribing responsive genes wherever they might be in nuclei. Using primary human endothelial cells, chromosome conformation capture, and RNA fluorescence in situ hybridization, we show that TNF-alpha induces responsive genes to congregate in discrete “NF-kappa B factories” when transcribed. Some factories further specialize in transcribing responsive genes encoding micro-RNAs. As transforming growth factor beta also induces its responsive genes to co-associate, we suggest cytokines typically signal through analogous specialized factories.