In response to inflammatory stimuli, the transcription factor NF-κB promotes gene transcription. In Molecular Cell, Gaudet and colleagues use single-cell analysis to show that the transcription of NF-κB-dependent genes is determined by the change in abundance, not the absolute abundance, of the NF-κB subunit RelA in the nucleus. For tumor-necrosis factor–sensitive genes that are constitutively expressed and 'scaled up' or strictly inducible by NF-κB, the maximum change in the abundance of nuclear RelA is the strongest predictor of transcription. A computational model that includes a 'competitor' that is subject to self-repression and has variable DNA-binding affinities for target promoters relative to those of the transcriptionally competent NF-κB reproduces the transcription patterns observed experimentally: with high competitor affinity, the transcription of target genes is inducible, whereas with low competitor affinity, gene expression is constitutive. The NF-κB subunits p50 and p52, which form transcriptionally incompetent homodimers, and the NF-κB inhibitor Bcl-3 fit the profile for such competitors. Thus, variation in the relative expression of competitors can vary the expression of 'hard-wired' promoters in various cell types.

Mol. Cell 53, 867–879 (2014)