Deficient activation of heat shock gene transcription in embryonal carcinoma cells.

Heat shock protein (HSP) synthesis cannot be induced by stress in the cleavage stage embryos of many different species. For instance, no HSP synthesis can be induced in the mouse embryo before the formation of the blastocyst. Similarly, HSP synthesis is not stress inducible in some embryonal carcinoma (EC) cell lines such as PCC4 and PCC7 S-1009 (1009). We show that RNAs coding for the major stress inducible murine heat shock protein, HSP68, do not accumulate in PCC4 or 1009 EC cells in response to a stress. Using an in vitro nuclear transcription assay, we demonstrate that the transcription of the corresponding genes is not activated after a stress. A specific gene switch-off due to DNA methylation or chromatin conformation is unlikely to account for this result. Indeed, stress does not promote the activation of the heterologous Drosophila HSP70 heat shock promoter in transfection assays of these cells. In contrast, the same promoter, like endogenous HSP synthesis, becomes stress inducible in 1009 cells after in vitro differentiation. This suggests that, in contrast to differentiated cells, these EC cells, and maybe the very early mouse embryonic cells, could lack a transacting activating transcription factor or contain a repressor.