TY - JOUR
T1 - Gene-specific requirement of a nuclear protein, IκB-ζ, for promoter association of inflammatory transcription regulators
AU - Yamazaki, Soh
AU - Matsuo, Susumu
AU - Muta, Tatsushi
AU - Yamamoto, Masahiro
AU - Akira, Shizuo
AU - Takeshige, Koichiro
PY - 2008/11/21
Y1 - 2008/11/21
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M802148200
DO - 10.1074/jbc.M802148200
M3 - Article
C2 - 18824552
AN - SCOPUS:57749084605
VL - 283
SP - 32404
EP - 32411
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 47
ER -