A Pituitary-Specific Factor Interacts with an Upstream Promoter Element in the Rat Growth Hormone Gene*

Abstract

The expression of the rat GH (rGH) gene is limited to the anterior pituitary. Using a DNase I footprinting assay, we have sought to identify specific protein-DNA interactions in the rGH 5'-flanking DNA that may be important in conferring tissue-specific use of the rGH promoter. We have identified a nuclear factor from rGH-secreting GC (rat pituitary) cells which interacts in the rGH 5'-flanking DNA between positions -94 to -62 relative to the start site of rGH gene transcription. This factor, which we have named GC1, is undetectable in nuclear extracts of non-rGH-producing rat fibroblast (Rat-2), or HeLa cells. Mutation of the GC1 binding region in the rGH 5'-flanking DNA results in only a small (30%) decrease in the ability of the rGH promoter to drive the expression of a linked marker gene when transfected into GC cells. GC1 represents, therefore, a novel type of promoter binding factor which is gene-specific and whose distribution is tissue-specific, but which is nonessential for the basal expression of its linked gene. Such a factor may, however, play a role in the modulation of rGH gene expression either through its interaction with other regulatory proteins or ligands or after enzyme modification.