Identification of a transactivation function in the progesterone receptor that interacts with the TAFII110 subunit of the TFIID complex

Abstract

Transcriptional activation of target genes by the human progesterone receptor is thought to involve direct or indirect protein-protein interactions between the progesterone receptor and general transcription factors. A key role in transcription plays the general transcription factor TFIID, a multiprotein complex consisting of the TATA-binding protein and several tightly associated factors (TAFs). TAFs have been shown to be required for activated transcription and are, thus, potential targets of activator proteins. Using in vitro interaction assays, we could identify specific interactions between the progesterone receptor and the TATA-binding protein-associated factor dTAFII110. The dTAFII110 domain responsible for the interaction is distinct from that reported to suffice for binding to Sp1. Somewhat surprisingly, deletion analysis indicated that the previously identified activation functions 1 and 2 of the progesterone receptor are not required for this interaction but pointed to an important role of the DNA binding domain. In cotransfection experiments and an in vitro transcription assay, the DNA binding domain of the progesterone receptor displayed significant activation potential. These findings, taken together, suggest that an interaction between the progesterone receptor and TAFII110 may represent an important step in the mechanism of activation.