ATTENUATION OF THE HEAT-SHOCK RESPONSE IN HELA-CELLS IS MEDIATED BY THE RELEASE OF BOUND HEAT-SHOCK TRANSCRIPTION FACTOR AND IS MODULATED BY CHANGES IN GROWTH AND IN HEAT-SHOCK TEMPERATURES
ATTENUATION OF THE HEAT-SHOCK RESPONSE IN HELA-CELLS IS MEDIATED BY THE RELEASE OF BOUND HEAT-SHOCK TRANSCRIPTION FACTOR AND IS MODULATED BY CHANGES IN GROWTH AND IN HEAT-SHOCK TEMPERATURES
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DOI：
10.1101/gad.5.11.2117
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发表时间：
1991-11-01
影响因子：
10.5
通讯作者：
MORIMOTO, RI
中科院分区：
文献类型：
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作者：
ABRAVAYA, K;PHILLIPS, B;MORIMOTO, RI
当海拉S3细胞遭受持续的42℃热激时，热激转录因子（HSF）的激活以及热激基因hsp70、hsp89 -α和hsp60的转录激活是瞬时的，在热激40 - 60分钟时达到峰值，然后减弱。我们利用体内基因组足迹法证明，hsp70转录的减弱是由结合在hsp70基因启动子热激元件（HSE）上的HSF的释放所介导的。体内结合的HSF的释放速率比根据体外解离测量所预测的要高。只有当采用温和的热激温度（42℃）时，HSF激活和热激基因转录才会减弱；将热激温度提高1℃会引发更高水平的激活，且在4小时的热激过程中不会减弱。令人惊讶的是，在热激前改变细胞生长的温度会调节对给定热激温度的反应幅度和时间模式。这一发现表明，HSF不是直接感知温度，而是可能对生长温度和热激温度之间差异的大小有反应。
When HeLa S3 cells are subjected to a continuous 42-degrees-C heat shock, activation of heat shock transcription factor (HSF) and transcriptional activation of the heat shock genes hsp70, hsp89-alpha, and hsp60 is transient, peaking at 40-60 min of heat shock, and then attenuating. We have used in vivo genomic footprinting to demonstrate that attenuation of hsp70 transcription is mediated by release of bound HSF from the heat shock element (HSE) of the hsp70 gene promoter. Release of bound HSF in vivo occurs at a higher rate than would be predicted from in vitro measurements of dissociation. Attenuation of HSF activation and heat shock gene transcription occurs only when mild heat shock temperatures are employed (42-degrees-C); increasing the heat shock temperature by 1-degrees-C elicits a much higher level of activation, which does not attenuate during a 4-hr heat shock. Surprisingly, altering the temperature at which cells are grown prior to heat shock modulates the magnitude and temporal pattern of the response to a given heat shock temperature. This finding suggests that HSF does not sense temperature directly but, instead, may be responsive to the magnitude of the difference between growth and heat shock temperatures.