Protein-binding elements in the proximal parotid secretory protein gene enhancer essential for salivary-gland-specific expression

The murine parotid secretory protein (PSP) gene is expressed at high levels in the parotid gland and at lower levels in the sublingual gland. A proximal enhancer core necessary for tissue-specific expression was identified previously, and it was demonstrated that one element, parotid gland element I (PGE I), exhibited specific binding of parotid gland nuclear proteins. In the present study, we demonstrate that a related adjacent element, PGE II, which binds nuclear proteins in a much less tissue-restricted manner, is able to compete with PGE I for binding of parotid-gland-specific factors. The functional significance of PGE I and PGE II was examined in transgenic mice. Deletion of PGE II reduced transgene expression only in the parotid gland, whereas deletion of PGE I appeared to reduce expression in both of the PSP-expressing salivary glands. Combined deletion of PGE I and PGE II reduced expression below the limit of detection. Thus PGE I and PGE II are functionally important salivary-gland-specific binding elements that are necessary for the salivary-gland-specific expression of a PSP minigene in transgenic mice.