DELINEATION OF A SMALL REGION WITHIN THE MAJOR TRANSACTIVATION DOMAINOF THE HUMAN GLUCOCORTICOID RECEPTOR THAT MEDIATES TRANSACTIVATION OFGENE-EXPRESSION

Previous deletion analysis localized the major transactivation functio n of the human glucocorticoid receptor to a 185-amino acid segment clo se to the N terminus of the receptor protein. This region was named ta u 1 [Hollenberg, S. M. & Evans, R. M. (1988) Cell 55, 899-906]. To del ineate the smallest active region within tau 1, we have systematically tested the transactivation capacity of deletion derivatives of the ta u 1 domain, fused to the glucocorticoid receptor DNA-binding domain, i n yeast cells. Internal scanning deletions suggested that residues nea r the C terminus of tau 1 are most important for activity. Deletions o f N terminal and C-terminal sequences identified a tau 1 amino acid '' core'' region near the C terminus of tau 1 that is crucial for tau 1 f unction. Small peptide fragments containing the tau 1 core region are competent for transactivation, while regions outside the tau 1. core a re not active. We have previously demonstrated that the intact tau 1 d omain squelches the activity of a minimal promoter in vivo and in vitr o, suggesting involvement of interactions with a component/components of the basal transcription machinery in the mechanism of transactivati on. This activity was maintained in the tau 1 core containing segments .