ACTIVATION OF TRANSCRIPTION BY PROGESTERONE-RECEPTOR INVOLVES DEREPRESSION OF ACTIVATION FUNCTIONS BY A COFACTOR

Hormone-induced progesterone receptors (PR) bound to response elements stimulate transcription initiation at target promoters through a mech anism that presumably involves cofactors or coactivators. To allow ide ntification of such cofactors of transcriptional activation in a funct ional assay, we have established a reconstituted transcription system that is characterized by a specific loss of responsiveness to purified baculovirus-expressed wild type PR. In contrast to wild type PR, a C- terminally truncated PR mutant displayed strong activation potential i n this system. As the purified recombinant full-length PR is capable o f DNA binding, our results suggest that C-terminal sequences of PR med iate a cis-repression of N-terminal activation functions. Moreover, us ing this PR-nonresponsive transcription system, we identified and part ially purified an activity from rat liver, termed COPRA (cofactor of P R activation), that restores transactivation by full-length PR. Charac terization of COPRA revealed that this cofactor exhibits activator spe cificity and is not involved in basal transcription. We postulate that COPRA acts by relieving the repression of activation functions mediat ed by C-terminal sequences.