Transcriptional repression by nuclear receptors: mechanisms and role in disease

Go-repressor proteins mediate transcriptional repression by nuclear recepto rs in the absence of ligand. The identification of a co-repressor-receptor interaction motif, and the finding that corepressors and co-activators comp ete for the same site on the receptor, suggests a simple mechanism for the switch from repression to activation upon ligand binding. Defects in this m echanism result in dominant-negative receptors that repress transcription. Such receptors have been implicated in several clinically important disease s, including thyroid hormone resistance and diabetes mellitus.