NOVEL SALIVARY-GLAND SPECIFIC BINDING-ELEMENTS LOCATED IN THE PSP PROXIMAL ENHANCER CORE

The murine parotid secretory protein (PSP) gene is expressed selective ly at high levels in parotid and sublingual salivary glands. Previousl y, the transcriptional activity of a PSP mini-gene, called Lama, was s hown to be dependent on a 1.5 kb region located 3 kb upstream of the t ranscription start site. Here, functional studies in transgenic mice d emonstrate that this proximal regulatory region has properties of a pa rotid and sublingual gland specific enhancer. Protein-binding experime nts identify multiple sequence-specific binding complexes spanning the entire 1.5 kb enhancer region. Several sequence elements bound specif ically by parotid and/or sublingual gland nuclear extracts, including consensus binding elements for previously described transcription fact ors as well as novel binding elements are located in the proximal enha ncer region, A deletion analysis of the enhancer region in transgenic mice identified a core sequence of 700 bp, This region contains five e lements bound specifically by nuclear proteins isolated from the PSP-e xpressing parotid and sublingual glands. Two of these elements, denote d parotid gland element I (PGE I) and sublingual gland element I (SLE I), are novel salivary gland specific binding elements, bound uniquely by parotid and sublingual gland nuclear extracts, respectively.