Hsp70 and Hsc70 are preferentially expressed in differentiated epithelial cells in normal human endometrium and ectocervix

Two highly related 70K heat shock proteins, encoded by the hsc70 and hsp70 genes, are located in the nucleocytoplasmic compartment of mammalian cells. In contrast to rodent cell lines, which express Hsp70 only when stressed, many human cell lines constitutively express Hsp70. The degree to which this reflects constitutive expression of Hsp70 in normal human tissues has not been extensively examined. In this study, we show by immunoblotting that human Hsp70 is constitutively expressed in the ovary, cervix, and endometrium and, by immunohistochemical analysis using Hsp70- and Hsc70-specific antibodies, that Hsp70 and Hsc70 are expressed in distinctive and predominantly overlapping patterns in the cervix and endometrium. In these two tissues, the highest levels of both proteins are seen in differentiated, non-proliferating epithelial cells, which is surprising in light of previous studies suggesting growth stimulation of hsp70 gene expression. These observations sugest the possibility that in certain human tissues, basal expression of the hsp70 and hsc70 genes is coregulated.     

Functional dissection of an early Drosophila chorion gene promoter: expression throughout the follicular epithelium is under spatially composite regulation.

We have fused various DNA sequences located upstream of the Drosophila melanogaster s36 chorion gene TATA box to a heterologous basal promoter and reporter gene (hsp70/lacZ). The expression of these constructs, following P-element-mediated germline transformation, was examined in 144 independent lines by histological staining of dissected ovaries for beta-galactosidase activity. A short 84 bp segment of the proximal 5' flanking DNA was sufficient to confer a wild-type gene expression pattern, including temporal specificity for early choriogenic follicles. Surprisingly, initial expression was very localized at the anterior and posterior poles of the follicle. The downstream half of that DNA segment permitted expression at both poles, but especially at the anterior tip, while the upstream half only favored expression in the posterior pole; these results suggested the existence of multiple, spatially specific cis-regulatory elements. When the proximal 84 bp segment was placed 1.5 kb upstream of the basal promoter, beta-galactosidase activity was observed in an altered spatial pattern, indicating that the cis-regulatory element(s) that favor expression in the posterior half of the follicle are position independent, while the element(s) that favor expression elsewhere in the follicle are position sensitive. A distal regulatory segment containing redundant DNA element(s) specific for expression in the anterior pole was identified much further upstream of s36. Thus, the expression of this chorion gene throughout the follicular epithelium is actually composite, occurring in distinct spatial domains under the control of corresponding DNA elements.     

Transcriptional regulation of an hsp70 heat shock gene in the yeast Saccharomyces cerevisiae.

The yeast Saccharomyces cerevisiae contains three heat-inducible hsp70 genes. We have characterized the promoter region of the hsp70 heat shock gene YG100, that also displays a basal level of expression. Deletion of the distal region of the promoter resulted in an 80% drop in the basal level of expression without affecting expression after heat shock. Progressive-deletion analysis suggested that sequences necessary for heat-inducible expression are more proximal, within 233 base pairs of the initiation region. The promoter region of YG100 contains multiple elements related to the Drosophila melanogaster heat shock element (HSE; CnnGAAnnT TCnnG). Deletion of a proximal promoter region containing one element, HSE2, eliminated most of the heat-inducible expression of YG100. The upstream activation site (UAS) of the yeast cytochrome c gene (CYC1) can be substituted by a single copy of HSE2 plus its adjoining nucleotides (UASHS). This hybrid promoter displayed a substantial level of expression before heat shock, and the level of expression was elevated eightfold by heat shock. YG100 sequences that flank UASHS inhibited basal expression of UASHS in the hybrid promoter but not its heat-inducible expression. This inhibition of basal UASHS activity suggests that negative regulation is involved in modulating expression of this yeast heat shock gene.