A pituitary-specific factor interacts with an upstream promotor element in the rat growth hormone gene.
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.
Catanzaro
D F
DF
Department of Biological Sciences, University of Sydney, New South Wales, Australia.
West
B L
BL
Baxter
J D
JD
Reudelhuber
T L
TL
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D003850:Deoxyribonuclease I / Q000032:analysis; D005260:Female; D005347:Fibroblasts / Q000032:analysis; D013006:Growth Hormone / Q000235:genetics*; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D008099:Liver / Q000032:analysis; D008969:Molecular Sequence Data; D010902:Pituitary Gland / Q000166:cytology / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D051381:Rats; D002583:Uterine Cervical Neoplasms / Q000032:analysis
D006133:Growth Substances; D013006:Growth Hormone; D003850:Deoxyribonuclease I