Class-specific regulation of pro-inflammatory genes by MyD88 pathways and IkappaBzeta.
Toll-like receptors trigger the induction of primary response genes via MyD88-mediated activation of NF-kappaB and other transcription factors. These factors then act in concert with primary response gene products to induce secondary response genes. Although the MyD88 pathway is important for the expression of both primary and secondary response genes, we show that the recruitment of NF-kappaB, RNA polymerase, and the TATA-binding protein is MyD88-dependent only at secondary response genes. This selective dependence correlates with the fact that MyD88 is required for nucleosome remodeling and histone H3K4 trimethylation at secondary response promoters, whereas rapidly induced primary response promoters are assembled into poised MyD88-independent chromatin structures. At a subset of secondary response promoters, IkappaBzeta was identified as a selective regulator of H3K4 trimethylation and preinitiation complex assembly after nucleosome remodeling. These mechanistic distinctions advance our understanding of the diverse molecular cascades that underlie the differential regulation of pro-inflammatory genes.
Kayama
Hisako
H
Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
Ramirez-Carrozzi
Vladimir R
VR
Yamamoto
Masahiro
M
Mizutani
Taketoshi
T
Kuwata
Hirotaka
H
Iba
Hideo
H
Matsumoto
Makoto
M
Honda
Kenya
K
Smale
Stephen T
ST
Takeda
Kiyoshi
K
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002478:Cells, Cultured; D042002:Chromatin Assembly and Disassembly; D004265:DNA Helicases / Q000378:metabolism; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008745:Methylation; D051379:Mice; D008957:Models, Genetic; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D009707:Nucleosomes / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D006657:Histones; D018836:Inflammation Mediators; D053594:Myeloid Differentiation Factor 88; C485947:Nfkbiz protein, mouse; D009687:Nuclear Proteins; D009707:Nucleosomes; D014157:Transcription Factors; C513194:Smarca4 protein, mouse; D004265:DNA Helicases; D008239:Lysine