Class-specific regulation of pro-inflammatory genes by MyD88 pathways and IκBζ
Class-specific regulation of pro-inflammatory genes by MyD88 pathways and IκBζ
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DOI：
10.1074/jbc.m709965200
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发表时间：
2008-05-02
影响因子：
4.8
通讯作者：
Takeda, Kiyoshi
中科院分区：
文献类型：
--
作者：
Kayama, Hisako;Ramirez-Carrozzi, Vladimir R.;Takeda, Kiyoshi
Toll样受体通过MyD88介导的核因子-kappaB和其他转录因子的激活，触发初级反应基因的诱导。然后，这些因子与初级反应基因产物协同作用，诱导次级反应基因。虽然MyD88通路对初级和次级反应基因的表达都很重要，但我们发现，核因子-kappa B、RNA聚合酶和TATA结合蛋白的募集只在次级反应基因上依赖于MyD88。这种选择性依赖与以下事实有关：MyD88是核小体重塑和组蛋白H3K4三甲基化所必需的次级反应启动子，而快速诱导的初级反应启动子组装成稳定的MyD88独立染色质结构。在次级反应启动子的一个子集上，I kappa B Zeta被认为是核小体重塑后H3K4三甲基化和预起始复合体组装的选择性调节因子。这些机制上的差异促进了我们对不同分子级联反应的理解，这些分子级联反应是促炎基因差异调控的基础。
Toll-like receptors trigger the induction of primary response genes via MyD88-mediated activation of NF-kappa B 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-kappa B, 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, I kappa B zeta 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.