Genome-wide analysis of human HSF1 signaling reveals a transcriptional program linked to cellular adaptation and survival
Genome-wide analysis of human HSF1 signaling reveals a transcriptional program linked to cellular adaptation and survival
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DOI：
10.1039/b606129j
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发表时间：
2006-12-01
影响因子：
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通讯作者：
Thomas, Russell S.
中科院分区：
文献类型：
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作者：
Page, Todd J.;Sikder, Devanjan;Thomas, Russell S.
尽管HSF1在细胞对蛋白毒性应激源的反应中起着重要作用，但对应激和非应激条件下人类HSF1信号网络的结构和功能知之甚少。在这项研究中，我们使用了染色质免疫沉淀微阵列分析和时程基因表达微阵列分析的组合，与和没有siRNA介导的抑制HSF1，以全面确定直接和间接调节的基因HSF1。启动子结合和基因表达之间的相关性是不显着的所有基因结合的HSF1，表明HSF1结合本身是不够的表达。然而，与启动子结合的相关性是显着的基因鉴定为HSF1调控后siRNA敲低。在热休克后由HSF1结合的启动子中，基因本体分析显示仅在与蛋白质折叠相关的类别中显着富集。相比之下，siRNA敲低后对扩展的HSF1信号网络的分析显示，与蛋白质折叠、抗凋亡、RNA剪接、泛素化等相关的各种类别中的富集，突出了由HSF1直接和间接调节的复杂转录程序。
Although HSF1 plays an important role in the cellular response to proteotoxic stressors, little is known about the structure and function of the human HSF1 signaling network under both stressed and unstressed conditions. In this study, we used a combination of chromatin immunoprecipitation microarray analysis and time course gene expression microarray analysis with and without siRNA-mediated inhibition of HSF1 to comprehensively identify genes regulated directly and indirectly by HSF1. The correlation between promoter binding and gene expression was not significant for all genes bound by HSF1, suggesting that HSF1 binding per se is not sufficient for expression. However, the correlation with promoter binding was significant for genes identified as HSF1-regulated following siRNA knockdown. Among promoters bound by HSF1 following heat shock, a gene ontology analysis showed significant enrichment only in categories related to protein folding. In contrast, analysis of the extended HSF1 signaling network following siRNA knockdown showed enrichment in a variety of categories related to protein folding, anti-apoptosis, RNA splicing, ubiquitinylation and others, highlighting a complex transcriptional program regulated directly and indirectly by HSF1.