Phosphorylation of the yeast heat shock transcription factor is implicated in gene-specific activation dependent on the architecture of the heat shock element
Phosphorylation of the yeast heat shock transcription factor is implicated in gene-specific activation dependent on the architecture of the heat shock element
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DOI：
10.1128/mcb.24.9.3648-3659.2004
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发表时间：
2004-05-01
影响因子：
5.3
通讯作者：
Sakurai, H
中科院分区：
文献类型：
--
作者：
Hashikawa, N;Sakurai, H
热休克转录因子（HSF）与热休克元件（HSE）结合并调节转录，HSE结构的差异提供了基因特异性和应激特异性反应。应激调节HSF的磷酸化状态，参与转录激活功能的激活和失活。酿酒酵母HSF的一个命名为CTM（C-末端调节剂）的结构域是激活含有非典型HSE但不含典型HSE的基因所必需的。在这里，我们表明，CTM功能是保守的酵母HSFs和必要的不仅为HSE特异性激活，但也为HSF在热休克后的过度磷酸化。此外，由于CTM突变的转录和磷酸化缺陷同时恢复了一组基因内抑制突变。因此，HSF的过度磷酸化与非典型HSE基因的激活相关，而与典型HSE基因的激活无关。CTM的功能在缺乏CE 2（酵母特异性阻遏结构域）的HSF衍生物中被规避。两者合计，我们认为，CTM通过CE 2，这使得HSF被热诱导磷酸化，并假定磷酸化是一个先决条件的激活剂功能的HSF时，它结合到一个非典型的HSE抑制。
Heat shock transcription factor (HSF) binds to the heat shock element (HSE) and regulates transcription, where the divergence of HSE architecture provides gene- and stress-specific responses. The phosphorylation state of HSF, regulated by stress, is involved in the activation and inactivation of the transcription activation function. A domain designated as CTM (C-terminal modulator) of the Saccharomyces cerevisiae HSF is required for the activation of genes containing atypical HSE but not typical HSE. Here, we demonstrate that CTM function is conserved among yeast HSFs and is necessary not only for HSE-specific activation but also for the hyperphosphorylation of HSF upon heat shock. Moreover, both transcription and phosphorylation defects due to CTM mutations were restored concomitantly by a set of intragenic suppressor mutations. Therefore, the hyperphosphorylation of HSF is correlated with the activation of genes with atypical HSE but is not involved in that of genes with typical HSE. The function of CTM was circumvented in an HSF derivative lacking CE2, a yeast-specific repression domain. Taken together, we suggest that CTM alleviates repression by CE2, which allows HSF to be heat-inducibly phosphorylated and presume that phosphorylation is a prerequisite for the activator function of HSF when it binds to an atypical HSE.