When the crem gene was discovered in 1991 from a murine pituitary cDNA library, three different CREM isoforms were described that are generated by alternative splicing processes [20]. CREM is structurally related to CREB, which had been identified a few years earlier, and at the time of its discovery was thought to exert dominant-negative effects on CREB-mediated gene transcription [20,21]. Over time, additional CREM isoforms have been described (>20 variants in humans), with some activating and some repressing gene transcription.
