An interaction between BRG1 and histone modifying enzymes mediates lipopolysaccharide-induced proinflammatory cytokines in vascular endothelial cells
An interaction between BRG1 and histone modifying enzymes mediates lipopolysaccharide-induced proinflammatory cytokines in vascular endothelial cells
复制标题
BRG1 和组蛋白修饰酶之间的相互作用介导血管内皮细胞中脂多糖诱导的促炎细胞因子
DOI：
10.1002/jcb.28595
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发表时间：
2019-08-01
影响因子：
4
通讯作者：
Xu, Yong
中科院分区：
文献类型：
--
作者：
Zhang, Yuanyuan;Yuan, Yibiao;Xu, Yong
血管炎症是人类许多疾病的罪魁祸首。然而，其潜在机制尚未明确阐明。在本研究中，我们研究了不同的表观遗传因素之间的相互作用，在脂多糖（LPS）诱导的促炎细胞因子在培养的血管内皮细胞的合成。我们报告说，在响应LPS治疗，NF-κ B是痛惜其目标启动子沿着染色质重塑蛋白BRG 1。伴随这些变化，三甲基化的H3 K9被清除，而三甲基化的H3 K4开始在NF-κ B靶启动子上积累。进一步的分析显示，LPS刺激导致H3 K9三-脱甲基酶JMJD 2A和H3 K4三甲基转移酶SET 1A相继募集到NF-κ B靶启动子。JMJD 2A介导的H3 K9去甲基化是SET 1A与NF-κ B靶启动子结合的先决条件。JMJD 2A和SET 1A通过维持NF-κ B的结合而对LPS诱导的促炎细胞因子的反式激活是必需的。重要的是，BRG 1协调了JMJD 2A和SET 1A的顺序招募和相互作用。总之，我们的数据揭示了一种新的表观遗传机制，有助于LPS诱导的血管炎症。
Vascular inflammation is the culprit for a host of human diseases. The underlying mechanism, however, is not definitively elucidated. In the present study, we investigated the interplay between different epigenetic factors during lipopolysaccharide (LPS) induced synthesis of proinflammatory cytokines in cultured vascular endothelial cells. We report that in response to LPS treatment, NF-kappa B was deplored to its target promoters along with the chromatin remodeling protein BRG1. Paralleling these changes trimethylated H3K9 became erased from while trimethylated H3K4 started to accumulate on the NF-kappa B target promoters. Further analysis revealed that LPS stimulation resulted in sequential recruitment of the H3K9 tri-demethylase JMJD2A and the H3K4 trimethyltransferase SET1A to the NF-kappa B target promoters. JMJD2A mediated-H3K9 demethylation served as a prerequisite for SET1A to bind to the NF-kappa B target promoters. Both JMJD2A and SET1A were essential for LPS-induced transactivation of proinflammatory cytokines by sustaining the binding of NF-kappa B. Of key importance, BRG1 coordinated the sequential recruit of and the interplay between JMJD2A and SET1A. In conclusion, our data unveil a novel epigenetic mechanism that contributes to LPS-induced vascular inflammation.