A DISTAL ACTIVATION DOMAIN IS CRITICAL IN THE REGULATION OF THE RAT ANDROGEN RECEPTOR GENE PROMOTER

The far upstream region of the rat androgen receptor (AR) gene has bee n cloned, and the nucleotide sequence up to -2656 bp established. Nest ed deletion mutants of rat AR 5' flanking sequences were ligated to th e luciferase reporter gene, and their promoter activities were examine d in transfected COS1 cells. Results show a critical cis-acting domain located between positions -960 and -940. Deletion of this cis element resulted in a greater than 90 % decrease in the promoter activity. A nuclear protein that specifically binds to this 21-nucleotide sequence was identified by gel mobility shift analysis. The -960/-940 cis elem ent has no identity to the binding sequence of any known transcription factor. Furthermore, the cognate binding protein is present in both r at and human (HeLa) cell nuclear extracts. We conclude that a novel tr ans-activator interacting at the -960/ -940 region plays a critical ro le in the regulation of AR gene expression.