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Nucleic Acids Research, 1995, Vol. 23, No. 10 1717-1721
© 1995

MOLECULAR BIOLOGY

A gene-type-specific enhancer regulates the carbamyl phosphate synthetase I promoter by cooperating with the proximal GAG activating element

Ing Swie Goping, Sonia Lamontagne, Gordon C. Shore and Mai Nguyen

Department of Biochemistry, Mclntyre Medical Sciences Building, McGill University Montreal, Quebec H3G 1Y6, Canada

*To whom correspondence should be addressed

Received February 9, 1995. Revised March 27, 1995. Accepted March 27, 1995.

The rat carbamyl phosphate synthetase I gene is expressed in two cell types: hepatocytes and epithelial cells of the intestinal mucosa. The proximal promoter contains a single activating element, GAG, two repres-sor elements (sites I and III) and an anti-repressor element (site II). Although these elements together exhibit the potential for complex regulation, they are unable to confer tissue-specific promoter activity. Here we have identified a cell-type-specific enhancer that lies 10 kllobases upstream of the promoter. Unexpectedly, the enhancer also functioned in a gene-type specific manner. The enhancer stimulated promoter activity exclusively through the proximal GAG element. Abrogation of GAG, either directly by mutation of GAG or indirectly by sites I and III repressors, abolished enhancer activation. Conversely, activation of the heterologous thymidlne kinase promoter by the enhancer required the introduction of GAG. The requirement for GAG, therefore, functions to constrain the enhancer to a specific target promoter.


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