ACTIVATION AND REPRESSION BY NUCLEAR HORMONE RECEPTORS - HORMONE MODULATES AN EQUILIBRIUM BETWEEN ACTIVE AND REPRESSIVE STATES

Transactivation-defective retinoid X and thyroid hormone receptors hav e been used to examine mechanisms of hormonal activation. Activation a nd repression of transcription by retinoid X and thyroid hormone recep tors are shown to be mediated by physically distinct and functionally independent regions of the hormone binding domain. Nevertheless, the a bility of receptors to respond to hormone requires communication betwe en both functional domains. Deletion of the hormone-dependent transact ivation function of the retinoid X receptor, the common subunit of het erodimeric nuclear receptors, significantly impairs hormone-dependent transcription by retinoic acid, thyroid hormone, and vitamin D recepto rs. The results indicate that receptors do not exist in static off and on conformations but that hormone alters an equilibrium between inact ive and active states.