CREM - A MASTER-SWITCH IN THE TRANSCRIPTIONAL RESPONSE TO CAMP

The CREM gene encodes both repressors and activators of cAMP-dependent transcription in a tissue and developmentally regulated manner. In ad dition, multiple and cooperative phosphorylation events regulate the f unction of the CREM proteins. CREM plays a key physiological and devel opmental role within the hypothalamic-pituitary axis. There is a funct ional switch in CREM expression during the development of male germ ce lls which is directed by the pituitary hormone FSH. The CREM protein i n germ cells is a powerful activator which appears to function as a ma ster-switch in the regulation of postmeiotic genes. CREM is inducible by activation of the cAMP signalling pathway with the kinetics of an e arly response gene. The induction is transient, cell-specific, does no t involve increased transcript stability and does not require protein synthesis. The subsequent decline in CREM expression requires de novo protein synthesis. The induced transcript encodes ICER and is generate d from an alternative, intronic promoter. ICER functions as a powerful repressor of cAMP-induced transcription, and represses the activity o f its own promoter, thus constituting a negative autoregulatory loop.