The role of heat shock transcription factor 1 in the genome-wide regulation of the mammalian heat shock response
The role of heat shock transcription factor 1 in the genome-wide regulation of the mammalian heat shock response
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DOI：
10.1091/mbc.e03-10-0738
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发表时间：
2004-03-01
影响因子：
3.3
通讯作者：
Myers, RM
中科院分区：
文献类型：
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作者：
Trinklein, ND;Murray, JI;Myers, RM
以往的研究表明，热休克转录因子1(HSF1)是哺乳动物细胞对热应激做出转录反应的主要转录因子。我们通过测量转录水平的变化和分析HSF1与候选热休克基因的启动子区域的结合来表征哺乳动物细胞的热休克反应，这些候选热休克基因是通过全基因组计算和实验相结合的方法选择的。我们发现许多热诱导基因在其启动子中都有与HSF1结合的位点(热休克元件，HSE)。令人惊讶的是，对于24个热诱导基因，我们没有检测到HSE和HSF1结合。此外，在182个具有可能的HSE序列的启动子中，我们仅检测到94个这些启动子与HSF1结合。同样出乎意料的是，我们发现了48个启动子中含有HSE的基因，这些基因与HSF1结合，但在我们检查的细胞类型中，热休克后没有显示出诱导作用。我们还研究了缺乏HSF1基因的小鼠成纤维细胞对热休克的转录反应。我们在这些细胞中发现了36个基因，这些基因既可以在野生型细胞中诱导，也可以在高温下诱导。这些结果提供了证据，证明HSF1并不调节热休克后积累的每一个转录本的诱导，我们的结果表明，一个独立的转录后机制调节相当数量的转录本的积累。
Previous work has implicated heat shock transcription factor 1 (HSF1) as the primary transcription factor responsible for the transcriptional response to heat stress in mammalian cells. We characterized the heat shock response of mammalian cells by measuring changes in transcript levels and assaying binding of HSF1 to promoter regions for candidate heat shock genes chosen by a combination of genome-wide computational and experimental methods. We found that many heat-inducible genes have HSF1 binding sites (heat shock elements, HSEs) in their promoters that are bound by HSF1. Surprisingly, for 24 heat-inducible genes, we detected no HSEs and no HSF1 binding. Furthermore, of 182 promoters with likely HSE sequences, we detected HSF1 binding at only 94 of these promoters. Also unexpectedly, we found 48 genes with HSEs in their promoters that are bound by HSF1 but that nevertheless did not show induction after heat shock in the cell types we examined. We also studied the transcriptional response to heat shock in fibroblasts from mice lacking the HSF1 gene. We found 36 genes in these cells that are induced by heat as well as they are in wild-type cells. These results provide evidence that HSF1 does not regulate the induction of every transcript that accumulates after heat shock, and our results suggest that an independent posttranscriptional mechanism regulates the accumulation of a significant number of transcripts.