Retinoids play a critical role in development, differentiation and homeostasis. Their effects on gene regulation are mediated by the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs). In our lab it has been established a cell-free transcription system utilising vaccinia virus expressed recombinant receptors competent for ligand binding. This system provided the first biochemical evidence that ligands govern the transcriptional activy of RXR/RAR by inducing conformational changes in the ligand binding domains.
Taking advantage of this system, we have designed a project to identify and clone co-activators that may help to elucidate how these factors act as 'molecular bridges' between the receptors and components of the basal transcription machinery. Ultimately, these studies may shed light on the combinatorial complexity which is necessary to account for the highly pleiotropic effects of the T3 and RA signals.