A hyper-dynamic equilibrium between promoter-bound and nucleoplasmic dimers controls NF-κB-dependent gene activity

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Abstract
Because of its very high affinity for DNA, NF‐κB is believed to make long‐lasting contacts with cognate sites and to be essential for the nucleation of very stable enhanceosomes. However, the kinetic properties of NF‐κB interaction with cognate sites in vivo are unknown. Here, we show that in living cells NF‐κB is immobilized onto high‐affinity binding sites only transiently, and that complete NF‐κB turnover on active chromatin occurs in less than 30 s. Therefore, promoter‐bound NF‐κB is in dynamic equilibrium with nucleoplasmic dimers; promoter occupancy and transcriptional activity oscillate synchronously with nucleoplasmic NF‐κB and independently of promoter occupancy by other sequence‐specific transcription factors. These data indicate that changes in the nuclear concentration of NF‐κB directly impact on promoter function and that promoters sample nucleoplasmic levels of NF‐κB over a timescale of seconds, thus rapidly re‐tuning their activity. We propose a revision of the enhanceosome concept in this dynamic framework.