Nuclear receptor coregulators: Judges, juries, and executioners of cellular regulation

In a little more than 10 years, nuclear receptor (NR) coregulators (coactivators and corepressors) have contributed to our present realization that a great level of sophistication exists in transcriptional regulation. Here, we discuss the implications of coregulators as versatile regulatory agents, influencing not only transcriptional initiation but also elongation, splicing, and translation. In addition to this, there is an increasing recognition that they also regulate a variety of biological processes outside of the nucleus. An important concept that we wish to emphasize is that coregulators are both targets and propagators of posttranslational modification (PTM) codes. This underlies a sophisticated epigenetic regulatory scheme from which a complex and dynamic mammalian phenotype emanates.