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

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