Christians E, Michel E, Adenot P, Mezger V, Rallu M, Morange M, Renard J P
Unité de Biologie du Développement, INRA, Jouy-en-Josas, France.
Mol Cell Biol. 1997 Feb;17(2):778-88. doi: 10.1128/MCB.17.2.778.
The mouse HSP70.1 gene, which codes for a heat shock protein (hsp70), is highly transcribed at the onset of zygotic genome activation (ZGA). This expression, which occurs in the absence of stress, is then repressed. It has been claimed that this gene does not exhibit a stress response until the blastocyst stage. The promoter of HSP70.1 contains four heat shock element (HSE) boxes which are the binding sites of heat shock transcription factors (HSF). We have been studying the presence and localization of the mouse HSFs, mHSF1 and mHSF2, at different stages of embryo development. We show that mHSF1 is already present at the one-cell stage and concentrated in the nucleus. Moreover, by mutagenizing HSE sequences and performing competition experiments (in transgenic embryos with the HSP70.1 promoter inserted before a reporter gene), we show that, in contrast with previous findings, HSE boxes are involved in this spontaneous activation. Therefore, we suggest that HSF1 and HSE are important in this transient expression at the two-cell stage and that the absence of typical inducibility at this early stage of development results mainly from the high level of spontaneous transcription of this gene during the ZGA.
小鼠热休克蛋白70.1(HSP70.1)基因编码一种热休克蛋白(hsp70),在合子基因组激活(ZGA)开始时高度转录。这种在无应激情况下发生的表达随后受到抑制。据称,该基因直到囊胚阶段才表现出应激反应。HSP70.1的启动子包含四个热休克元件(HSE)框,它们是热休克转录因子(HSF)的结合位点。我们一直在研究小鼠HSF(mHSF1和mHSF2)在胚胎发育不同阶段的存在情况和定位。我们发现mHSF1在单细胞阶段就已存在并集中在细胞核中。此外,通过诱变HSE序列并进行竞争实验(在将HSP70.1启动子插入报告基因之前的转基因胚胎中),我们发现,与之前的研究结果相反,HSE框参与了这种自发激活。因此,我们认为HSF1和HSE在两细胞阶段的这种瞬时表达中很重要,并且在发育早期缺乏典型的诱导性主要是由于该基因在ZGA期间的高水平自发转录。