Negative regulation by nuclear receptors: a plethora of mechanisms

Nuclear receptors are arguably the best understood transcriptional regulators. We know a great deal about the mechanisms through which they activate transcription in response to ligand binding and about the mechanisms through which they repress transcription in the absence of ligand. However, endocrine regulation often requires that ligand-bound receptors repress transcription of a subset of genes. An understanding of the mechanism for ligand-induced repression and how this differs from activation has proven elusive. A number of recent studies have directly or indirectly addressed this problem. Yet it seems the more evidence that accumulates, the more complex the mystery becomes.