Transcriptional activation by nuclear receptors

Transcriptional activation by nuclear receptors (NRs) involves the recruitment of distinct classes of co-activators and other transcription-related factors to target promoters in the chromatin environment of the nucleus. Chromatin has a general repressive effect on transcription, but also provides opportunities for NRs to regulate transcription by directing specific patterns of chromatin remodelling and histone modification. Ultimately, the transcription of hormone-regulated genes by NRs is critically dependent on co-ordinated physical and functional interactions among the receptors, chromatin, co-activators with chromatin-, histone- and factor-modifying activities, and the RNA polymerase II transcriptional machinery. In addition, several mechanisms exist to terminate or attenuate NR-dependent signalling, including modification, recycling, subcellular redistribution and degradation of the receptors or their associated cofactors. The complexity of NR-dependent transcription provides multiple targets for regulatory inputs, thus allowing each hormone-responsive cell to direct its transcriptional output in a physiologically appropriate manner.