Two Waves of Nuclear Factor κb Recruitment to Target Promoters

Proinflammatory stimuli induce the rapid and transient translocation of nuclear factor (NF)-κB 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-κB 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-κB sites accessible (promoters with regulated and late accessibility [RLA]). Our results suggest that a mechanism of specificity in NF-κB–dependent transcriptional responses relies on the ability of individual stimuli to make RLA promoters accessible to NF-κB before its rapid extrusion from the nucleus.