Wang Z, Lindquist S
Committee on Developmental Biology, The University of Chicago, Chicago, IL 60637, USA.
Development. 1998 Dec;125(23):4841-50. doi: 10.1242/dev.125.23.4841.
Hsp70 is a broadly conserved thermotolerance factor, but inhibits growth at normal temperatures and cannot be induced in early embryos. We report that in Drosophila embryos the temporal and spatial patterns of Hsp70 inducibility were unexpectedly complex, with striking differences between the soma and the germline. In both, regulation occurred at the level of transcription. During the refractory period for Hsp70 induction, HSF (heat-shock transcription factor) exhibited specific DNA-binding activity characteristic of activation in extracts of heated embryos. Remarkably, however, HSF was restricted to the cytoplasm in intact embryos even after heat shock. HSF moved from the cytoplasm to the nucleus in the absence of heat precisely when the capacity to induce Hsp70 was acquired (cycle 12 of the germline, cycle 13 in the soma). During oogenesis, Hsp70 inducibility was lost in nurse cells around stage 10, in a posterior-to-anterior gradient and HSF redistributed from nucleus to cytoplasm in the same spatiotemporal pattern. In a highly inbred derivative of the Samarkind strain, HSF moved into embryonic nuclei earlier than in our standard wild-type strain. Correspondingly, Hsp70 was inducible earlier, confirming that nuclear transport of HSF controls the inducibility of Hsp70 in early embryos. We also report for the first time the nuclear import patterns of two general transcription factors, RNA polymerase subunit Ilc and TATA binding protein (TBP). Both enter nuclei in a highly synchronous manner, independently of each other and of HSF. The import of TBP coincides with the first reported appearance of transcripts in the embryo. We suggest that the potentiation of general and heat shock-specific transcription in Drosophila embryos is controlled by the developmentally programmed relocalization of general and heat shock-specific transcription factors. Restricted nuclear entry of HSF represents a newly described mechanism for regulating the heat-shock response.
热休克蛋白70（Hsp70）是一种广泛保守的耐热因子，但在正常温度下会抑制生长，且在早期胚胎中无法被诱导。我们报告称，在果蝇胚胎中，Hsp70诱导的时空模式出人意料地复杂，体细胞和生殖系之间存在显著差异。在这两者中，调控都发生在转录水平。在Hsp70诱导的不应期，热休克转录因子（HSF）在受热胚胎提取物中表现出激活特有的特异性DNA结合活性。然而，值得注意的是，即使在热休克后，HSF在完整胚胎中仍局限于细胞质。在获得诱导Hsp70的能力时（生殖系的第12周期，体细胞的第13周期），HSF在无热的情况下从细胞质转移到细胞核。在卵子发生过程中，大约在第10阶段，滋养细胞中Hsp70的诱导能力以从后到前的梯度丧失，HSF以相同的时空模式从细胞核重新分布到细胞质。在撒马尔罕品系的一个高度近交衍生物中，HSF比我们的标准野生型品系更早进入胚胎细胞核。相应地，Hsp70更早被诱导，证实了HSF的核转运控制早期胚胎中Hsp70的诱导能力。我们还首次报告了两种通用转录因子，RNA聚合酶亚基Ilc和TATA结合蛋白（TBP）的核输入模式。两者以高度同步的方式进入细胞核，彼此独立且与HSF无关。TBP的输入与胚胎中首次报道的转录本出现时间一致。我们认为，果蝇胚胎中通用转录和热休克特异性转录的增强是由通用转录因子和热休克特异性转录因子的发育程序性重新定位控制的。HSF受限的核进入代表了一种新描述的调节热休克反应的机制。
