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首页> 外文期刊>Cytokine >Distinct, gene-specific effect of heat shock on heat shock factor-1 recruitment and gene expression of CXC chemokine genes.
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Distinct, gene-specific effect of heat shock on heat shock factor-1 recruitment and gene expression of CXC chemokine genes.

机译：热休克对热休克因子-1募集和CXC趋化因子基因的基因表达的不同的基因特异性作用。

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The heat shock (HS) response, a phylogenetically conserved ubiquitous response to stress, is generally characterized by the induced expression of heat shock protein (HSP) genes. Our earlier studies showed that the stress-activated transcription factor, heat shock factor-1 (HSF1), activated at febrile range or HS temperatures also modified expression of non-HSP genes including cytokine and chemokine genes. We also showed by in silico analysis that 28 among 29 human and mouse CXC chemokine genes had multiple putative heat shock response elements (HSEs) present in their gene promoters. To further determine whether these potential HSEs were functional and bound HSF1, we analyzed the recruitment of HSF1 to promoters of 5 human CXC chemokine genes (CXCL-1, 2, 3, 5 and 8) by chromatin immunoprecipitation (ChIP) assay and analyzed the effect of HS exposure on tumor necrosis factor-alpha (TNFalpha)-induced expression of these genes in human lung epithelial-like A549 cells. HSF1 ChIP analysis showed that HSF1 was recruited to all but one of these CXC chemokine genes (CXCL-3) and HS caused a significant increase in recruitment of HSF1 to one or multiple HSEs present in the promoters of CXCL-1, 2, 5 and 8 genes. However, the effect of HS exposure on expression of these genes showed a variable gene-specific effect. For example, CXCL8 expression was markedly enhanced (p<0.05) whereas CXCL5 expression was significantly repressed (p<0.05) in cells exposed to HS coincident with TNFalpha stimulation. In contrast, expression of CXCL1 and CXCL2, despite HSF1 recruitment to their promoters, was not affected by HS exposure. Our results indicate that some, if not all, putative HSEs present in the CXC chemokine gene promoters are functional and recruit HSF1 in vivo but the effects on gene expression are variable and gene specific. We speculate, the physical proximity and interactions of other transcription factors and co-regulators with HSF1 could be critical to determining the effects of HS on the expression of these genes.
机译：热休克（HS）响应是对压力的系统发育上普遍存在的应答，通常以热激蛋白（HSP）基因的诱导表达为特征。我们较早的研究表明，在高热范围或HS温度下激活的应激激活转录因子热休克因子1（HSF1）也修饰了非HSP基因的表达，包括细胞因子和趋化因子基因。我们还通过计算机分析显示，在29个人类和小鼠CXC趋化因子基因中，有28个在其基因启动子中存在多个假定的热休克反应元件（HSE）。为了进一步确定这些潜在的HSE是否具有功能性并与HSF1结合，我们通过染色质免疫沉淀（ChIP）分析了HSF1募集到5个人类CXC趋化因子基因（CXCL-1、2、3、5和8）的启动子，并分析了暴露对肿瘤坏死因子-α（TNFalpha）诱导的这些基因在人肺上皮样A549细胞中表达的影响。 HSF1 ChIP分析显示，除这些CXC趋化因子基因之一（CXCL-3）之外，HSF1均被募集，而HS导致HSF1募集至CXCL-1、2、5和CXCL-1启动子中存在的一种或多种HSE的显着增加。 8个基因。但是，HS暴露对这些基因表达的影响显示出可变的基因特异性作用。例如，在暴露于与TNFα刺激相一致的HS的细胞中，CXCL8表达显着增强（p ＜0.05），而CXCL5表达被显着抑制（p ＜0.05）。相反，尽管HSF1募集到其启动子，但CXCL1和CXCL2的表达不受HS暴露的影响。我们的结果表明，存在于CXC趋化因子基因启动子中的一些（如果不是全部）推定的HSE在体内具有功能并募集HSF1，但对基因表达的影响却是可变的且是基因特异性的。我们推测，HSF1与其他转录因子和共调节因子的物理接近性和相互作用可能对确定HS对这些基因表达的影响至关重要。

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