Developmentally regulated nuclear transport of transcription factors in Drosophila embryos enable the heat shock response.
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.
Wang
Z
Z
Committee on Developmental Biology, The University of Chicago, Chicago, IL 60637, USA.
Lindquist
S
S
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000502:physiology*; D004627:Embryonic Induction; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D000076249:Heat Shock Transcription Factors; D006358:Hot Temperature; D009866:Oogenesis; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; C053134:Hsf protein, Drosophila; D014157:Transcription Factors; D012321:DNA-Directed RNA Polymerases