Coactivation and corepression in transcriptional regulation by steroid/nuclear hormone receptors

Transcriptional regulation by steroid/nuclear receptors is the central theme of hormone action that controls key aspects of cell differentiation, development, and homeostasis. The molecular mechanisms of gene activation and repression by the receptors have been investigated extensively in recent years. Particularly, several new proteins involved in this signaling pathway have been identified, cloned, and demonstrated to modulate transcription in concert with nuclear receptors. In the absence of hormone, unliganded receptors interact with a family of transcriptional corepressors, including SMRT and N-CoR, which target histone deacetylases to establish a condensed and repressed chromatin structure. Upon hormone binding, the corepressor complex is replaced by a coactivator complex, containing SRC1/TIF2/RAC3 and CBP/p300, which target histone acetyltransferases to generate a transcriptionally accessible chromatin structure. These studies initiate a new era in the history of hormone research and provide novel entry points for understanding the mechanisms of transcriptional regulation by steroid/nuclear receptors.