Article
- The EMBO Journal (2006) 25, 798 - 810
- doi:10.1038/sj.emboj.7600977
Published online: 9 February 2006
Subject Category:
A hyper-dynamic equilibrium between promoter-bound and nucleoplasmic dimers controls NF-
B-dependent gene activity
Daniela Bosisio1,ab, Ivan Marazzi1,a, Alessandra Agresti2,a, Noriaki Shimizu3, Marco E Bianchi4 and Gioacchino Natoli5
- Institute for Research in Biomedicine, Bellinzona, Switzerland
- San Raffaele Scientific Institute, Milan, Italy
- Faculty of Integrated Arts and Sciences, Hiroshima University, Hiroshima, Japan
- San Raffaele University, Milan, Italy
- European Institute of Oncology, Milan, Italy
Correspondence to:
Marco E Bianchi, San Raffaele University, Via Olgettina 58, 20132, Milan, Italy. Tel.: +39 02 26434 763; Fax: +39 02 26434 861; E-mail: bianchi.marco@hsr.it
Gioacchino Natoli, Department of Experimental Oncology, European Institute of Oncology, Via Ripamonti 435, 20141, Milan, Italy. Tel.: +39 02 5748 9953; Fax: +39 02 5748 9851; E-mail: gioacchino.natoli@ifom-ieo-campus.it
aThese authors contributed equally to this work
bPresent address: General Pathology and Immunology, University of Brescia, Viale Europa 11, Brescia, Italy
Received 26 July 2005; Accepted 19 December 2005
Abstract
Because of its very high affinity for DNA, NF-
B 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-B interaction with cognate sites in vivo are unknown. Here, we show that in living cells NF-B is immobilized onto high-affinity binding sites only transiently, and that complete NF-B turnover on active chromatin occurs in less than 30 s. Therefore, promoter-bound NF-B is in dynamic equilibrium with nucleoplasmic dimers; promoter occupancy and transcriptional activity oscillate synchronously with nucleoplasmic NF-B and independently of promoter occupancy by other sequence-specific transcription factors. These data indicate that changes in the nuclear concentration of NF-B directly impact on promoter function and that promoters sample nucleoplasmic levels of NF-B over a timescale of seconds, thus rapidly re-tuning their activity. We propose a revision of the enhanceosome concept in this dynamic framework.
Keywords:
- enhanceosome,
- kinetic microscopy,
- NF-B,
- Rel,
- transcription
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