Nuclear receptor coregulators

Abstract

It has been postulated that nuclear receptors (NRs) regulate transcription via interactions with chromatin and the basal transcription machinery at the promoters of genes. Coregulators (coactivators or corepressors) are important in mediating these interactions and thereby modulating positive or negative receptor activity. A large number of putative coactivators have been isolated, several of which will be reviewed with respect to certain "criteria" initially proposed for coactivators. We will discuss, with reference to in vitro and in vivo experiments, the main steps in initiation that are influenced by coactivators: (1) initiation (e.g., SRC-1 family, CBP); (2) repetitive transcription (e.g., TRAPs/DRIPs); (3) RNA processing (PGC-1, etc); and (4) termination/turnover (E6-AP, etc). A variety of enzyme functions have been implicated in the coactivator complex including acetylase, methylase, ubiquitin ligase, kinase, and phosphatase activities. Moreover, coactivators and corepressors appear to exist in the steady-state cell as a series of multiprotein complexes referred to collectively as the " coregulatorsome". Different subcomplexes within the coregulatorsome may have different levels of preference for individual receptors or promoters, likely contributing to context-specific functions of NRs in target tissues.