Gene-specific requirement of a nuclear protein, IkappaB-zeta, for promoter association of inflammatory transcription regulators.
Expression of many inflammatory genes is induced through activation of the transcription factor NF-kappaB. In contrast to the advanced understanding of cytoplasmic control of NF-kappaB 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, IkappaB-zeta, and demonstrated that this molecule is indispensable for the expression of a group of NF-kappaB-regulated genes. In this study, we established a unique gene induction system, in which IkappaB-zeta is expressed independently of inflammatory stimuli, to specifically investigate the molecular basis underlying IkappaB-zeta-mediated gene activation. We show that in the presence of IkappaB-zeta other primary response genes are dispensable for the expression of the target secondary response genes. ChIP analyses revealed that IkappaB-zeta is required for stimulus-induced recruitment of NF-kappaB onto the target promoter in a gene-specific manner. Surprisingly, IkappaB-zeta is also necessary for the gene-selective promoter recruitment of another inflammatory transcription factor, C/EBPbeta, and the chromatin remodeling factor Brg1. We propose a new gene regulatory mechanism underlying the selective expression of inflammatory genes.
Yamazaki
Soh
S
Department of Molecular and Cellular Biochemistry, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, 812-8582, Japan. syamaz@mailserver.med.kyushu-u.ac.jp
Matsuo
Susumu
S
Muta
Tatsushi
T
Yamamoto
Masahiro
M
Akira
Shizuo
S
Takeshige
Koichiro
K
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002467:Cell Nucleus / Q000378:metabolism*; D005786:Gene Expression Regulation; D007249:Inflammation; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D008957:Models, Genetic; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C485947:Nfkbiz protein, mouse; D009687:Nuclear Proteins; D014157:Transcription Factors