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-kappa B. In contrast to the advanced understanding of cytoplasmic control of NF-kappa B 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, I kappa B-zeta, and demonstrated that this molecule is indispensable for the expression of a group of NF-kappa B-regulated genes. In this study, we established a unique gene induction system, in which I kappa B-zeta is expressed independently of inflammatory stimuli, to specifically investigate the molecular basis underlying I kappa B-zeta-mediated gene activation. We show that in the presence of I kappa B-zeta other primary response genes are dispensable for the expression of the target secondary response genes. ChIP analyses revealed that I kappa B-zeta is required for stimulus-induced recruitment of NF-kappa B onto the target promoter in a gene-specific manner. Surprisingly, I kappa B-zeta is also necessary for the gene-selective promoter recruitment of another inflammatory transcription factor, C/EBP beta, and the chromatin remodeling factor Brg1. We propose a new gene regulatory mechanism underlying the selective expression of inflammatory genes.