COUP-TF-II HOMODIMERS ARE FORMED IN PREFERENCE TO HETERODIMERS WITH RXR-ALPHA OR TR-BETA IN INTACT-CELLS

Chicken ovalbumin upstream promoter-transcription factor (COUP-TF) rep resses the transcriptional activity of a number of nuclear receptors, including that of retinoid receptors (RAR and RXR) and thyroid hormone receptors (TR). Since COUP-TF is capable of binding to DNA in vitro e ither as a homodimer or as a heterodimer with RXR or TR, it has not be en possible to distinguish between competitive DNA binding and heterod imer formation as a mechanism to account for the repression. Using a t wo-hybrid system we have investigated the dimerisation properties of C OUP-TF II in intact cells, In conditions where COUP-TF II homodimers a nd RXR alpha-RAR alpha heterodimers were formed we were unable to dete ct the formation of heterodimers between COUP-TF II and RXR alpha. Mor eover, we were unable to detect an interaction between COUP-TF II and RXR alpha on DNA, Similarly COUP-TF II homodimers and RXR alpha-TR bet a heterodimers. are favoured over COUP-TF II-TR beta heterodimers, We conclude that the formation of functionally inactive heterodimers is u nlikely to represent a general mechanism by which COUP-TF represses th e transcriptional activity of nuclear receptors and favour a model in which repression is mediated by COUP-TF homodimers competing for bindi ng to DNA.