DREAM-alpha CREM interaction via leucine-charged domains derepresses downstream regulatory element-dependent transcription

Protein kinase A-dependent derepression of the human prodynorphin gene is r egulated by the differential occupancy of the Dyn downstream regulatory ele ment (DRE) site. Here, we show that a direct protein-protein interaction be tween DREAM and the CREM repressor isoform, alpha CREM, prevents binding of DREAM to the DRE and suggests a mechanism for cyclic AMP-dependent derepre ssion of the prodynorphin gene in human neuroblastoma cells. Phosphorylatio n in the kinase-inducible domain of alpha CREM is not required for the inte raction, but phospho-alpha CREM shows higher affinity for DREAM. The intera ction with alpha CREM is independent of the Ca2+-binding properties of DREA M: and is governed by leucine-charged residue-rich domains located in both alpha CREM and DREAM. Thus, our results propose a new mechanism for DREAM-m ediated derepression that can operate independently of changes in nuclear C a2+.