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

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. [ABSTRACT FROM AUTHOR]