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

Daniela Bosisio, Ivan Marazzi, Alessandra Agresti, Noriaki Shimizu, Marco E. Bianchi, Gioacchino Natoli

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)798-810
Number of pages13
JournalEMBO Journal
Volume25
Issue number4
DOIs
Publication statusPublished - Feb 22 2006

Keywords

  • Enhanceosome
  • Kinetic microscopy
  • NF-κB
  • Rel
  • Transcription

ASJC Scopus subject areas

  • Cell Biology
  • Genetics

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