The Journal of Experimental Medicine
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Published online 18 June 2001.
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© The Rockefeller University Press, 0022-1007/2001/6/1351/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 12, June 18, 2001 1351-1360

Original Article

Two Waves of Nuclear Factor {kappa}b Recruitment to Target Promoters

Simona Saccania, Serafino Pantanoa, and Gioacchino Natolia

a Institute for Research in Biomedicine, CH6501 Bellinzona, Switzerland
Institute for Research in Biomedicine, Via Vela 6, CH6501 Bellinzona, Switzerland.41-91-820030541-91-8200318

gionatoli{at}hotmail.com

Proinflammatory stimuli induce the rapid and transient translocation of nuclear factor (NF)-{kappa}B to the nucleus, where it activates transcription from several genes, including those encoding inflammatory cytokines and chemokines, adhesion molecules, and cytoprotective proteins. Using chromatin immunoprecipitation, we show that after an acute stimulation two distinct waves of NF-{kappa}B recruitment to target promoters occur: a fast recruitment to constitutively and immediately accessible (CIA) promoters and a late recruitment to promoters requiring stimulus-dependent modifications in chromatin structure to make NF-{kappa}B sites accessible (promoters with regulated and late accessibility [RLA]). Our results suggest that a mechanism of specificity in NF-{kappa}B–dependent transcriptional responses relies on the ability of individual stimuli to make RLA promoters accessible to NF-{kappa}B before its rapid extrusion from the nucleus.

Key Words: NF-{kappa}B • Rel • histone acetylation • chromatin immunoprecipitation • lipopolysaccharide

S. Saccani and S. Pantano contributed equally to this work.

Abbreviations used in this paper: ChIP, chromatin immunoprecipitation; CIA, constitutively and immediately accessible; EMSA, electrophoretic mobility shift assay; I{kappa}B, inhibitor of NF-{kappa}B; MCP-1, macrophage chemoattractant protein 1; MIP-2, macrophage inflammatory protein 2; MnSOD, manganese superoxide dismutase; NF-{kappa}B, nuclear factor {kappa}B; RANTES, regulated upon activation, normal T cell expressed and secreted; RLA, regulated and late accessibility.

© 2001 The Rockefeller University Press


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