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| Subject Categories: Chromatin & Transcription |
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| The EMBO Journal
(2006) 25, 798–810, doi:10.1038/sj.emboj.7600977 Published online 9 February 2006 |
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A hyper-dynamic equilibrium between promoter-bound and nucleoplasmic dimers controls NF- B-dependent gene activity |
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| Daniela Bosisio1, 6, 7, Ivan Marazzi1, 6, Alessandra Agresti2, 6, Noriaki Shimizu3, Marco E Bianchi4 and Gioacchino Natoli5 |
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1 Institute for Research in Biomedicine, Bellinzona, Switzerland 2 San Raffaele Scientific Institute, Milan, Italy 3 Faculty of Integrated Arts and Sciences, Hiroshima University, Hiroshima, Japan 4 San Raffaele University, Milan, Italy 5 European Institute of Oncology, Milan, Italy To whom correspondence should be addressed 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 6 These authors contributed equally to this work 7 Present address: General Pathology and Immunology, University of Brescia, Viale Europa 11, Brescia, Italy Received 26 July 2005; Accepted 19 December 2005; Published online 9 February 2006. |
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| Abstract |
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| 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. |
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| Keywords: enhanceosome, kinetic microscopy, NF-B, Rel, transcription |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated NEWS AND VIEWSShigella rewrites host transcriptional responses Nature Immunology News and Views (01 Jan 2007) RESEARCHArginine methyltransferase CARM1 is a promoter-specific regulator of NF-κB-dependent gene expression The EMBO Journal Article (12 Jan 2005) |
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