| Autor: |
Farmerie, Todd A., Abbud, Rula A., Budworth, Paul R., Clay, Colin M., Keri, Ruth A., McDowell, Karen J., Wolfe, Michael W., Nilson, John H. |
| Zdroj: |
Biology of Reproduction; November 1997, Vol. 57 Issue: 5 p1104-1114, 11p |
| Abstrakt: |
The equine glycoprotein hormone α-subunit gene is expressed in both pituitary and placenta, unlike that of all other nonprimate mammals studied, in which expression is limited to pituitary. Previous studies of the 5'-flanking region of the equine α-subunit promoter have revealed unique characteristics as well as similarities with the human α-subunit promoter, which demonstrates a similar pattern of tissue-specific expression. We have cloned and sequenced the equine α-subunit gene and have used tissue culture systems and transgenic mice to characterize its expression. Unlike the human promoter, the cloned equine et-subunit promoter failed to direct trophoblast-specific expression in either tissue culture or transgenic mouse models, suggesting an entirely different mechanism for expression. In contrast, the equine α-subunit promoter was able to direct gonadotroph expression in both tissue culture and transgenic mouse models. In αT3–1 cells, 550 base pair (bp) was sufficient for expression. This expression involves promoter elements identified in other species as playing a role in gonadotroph expression, but mutation of these elements reveals differences in their relative contributions to promoter activity. In mice, 2800 bp of 5'-flanking sequence allowed specific expression in gonadotrophs but not in thyrotrophs or placenta. The pattern of estrogen regulation observed in transgenic mice matched neither the repression that has been observed with human and bovine α-subunit promoters in transgenic mice nor the stimulation in mRNA levels reported in mares, suggesting a unique mechanism that is not recapitulated in the transgenic model. Thus the equine α-subunit promoter uses a combination of conserved and unique features of gene regulation to direct its pattern of tissue-specific expression. |
| Databáze: |
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