Gene-specific Requirement of a Nuclear Protein, IκB-ζ, for Promoter Association of Inflammatory Transcription Regulators

Expression of many inflammatory genes is induced through activation of the transcription factor NF-κB. In contrast to the advanced understanding of cytoplasmic control of NF-κB activation, its regulation in the nucleus has not been fully understood despite its importance in selective gene expression...

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Veröffentlicht in:The Journal of biological chemistry 2008-11, Vol.283 (47), p.32404-32411
Hauptverfasser: Yamazaki, Soh, Matsuo, Susumu, Muta, Tatsushi, Yamamoto, Masahiro, Akira, Shizuo, Takeshige, Koichiro
Format: Artikel
Sprache:eng
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Zusammenfassung:Expression of many inflammatory genes is induced through activation of the transcription factor NF-κB. In contrast to the advanced understanding of cytoplasmic control of NF-κB activation, its regulation in the nucleus has not been fully understood despite its importance in selective gene expression. We previously identified an inducible nuclear protein, IκB-ζ, and demonstrated that this molecule is indispensable for the expression of a group of NF-κB-regulated genes. In this study, we established a unique gene induction system, in which IκB-ζ is expressed independently of inflammatory stimuli, to specifically investigate the molecular basis underlying IκB-ζ-mediated gene activation. We show that in the presence of IκB-ζ other primary response genes are dispensable for the expression of the target secondary response genes. ChIP analyses revealed that IκB-ζ is required for stimulus-induced recruitment of NF-κB onto the target promoter in a gene-specific manner. Surprisingly, IκB-ζ is also necessary for the gene-selective promoter recruitment of another inflammatory transcription factor, C/EBPβ, and the chromatin remodeling factor Brg1. We propose a new gene regulatory mechanism underlying the selective expression of inflammatory genes.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M802148200