DREAM regulates insulin promoter activity through newly identified DRE element

Abstract

Downstream regulatory element antagonist modulator (DREAM) protein is a 31 kDa Ca 2+-regulated transcriptional repressor. It functions as a silencer of the gene transcription. In low intracellular free Ca 2+ concentration DREAM tightly binds to the downstream regulatory element (DRE) of gene promoter and impedes the transcription. In higher Ca 2+ concentrations DREAM binds Ca 2+ and disconnects from DRE of the gene promoter enabling transcription. We report that DREAM is expressed in different human tissues including the pancreas, where it is located in the islets of Langerhans. Location of DREAM in RIN-F5 cells in cultures is restricted to the nucleus and membranes and changes after increased Ca 2+ -levels. The proteins dissociate from dimmers to monomers and translocate out of the nucleus. The expression of DREAM in β-cells in the islets of Langerhans regulates the promoter activity of the insulin gene by directly interacting with the sequence located between +52 bp and +81 bp downstream of the transcriptional start site of the promoter. Our results provide evidence for the existence of DRE sequence in the insulin gene promoter. It is suggested that DREAM is a repressor of insulin gene transcription, whose effect is mediated by direct binding to DRE sequence.

Insight into the Interaction between Neuronal Calcium Sensors and Insulin

“…The insulin-stimulated translocation of GLUT-4 is associated with glucose clearance from plasma and defects are associated with insulin resistance and diabetes [14,15]. Along with NCS-1, other NCS proteins are also implicated in insulin regulation and diabetes [16,17]. Downstream regulatory element (DRE) antagonist modulator (DREAM) binds to DRE of insulin gene transcription promotor as dimmer under low Ca 2+ levels and released at high Ca 2+ levels inside the nucleus [16].…”

“…Along with NCS-1, other NCS proteins are also implicated in insulin regulation and diabetes [16,17]. Downstream regulatory element (DRE) antagonist modulator (DREAM) binds to DRE of insulin gene transcription promotor as dimmer under low Ca 2+ levels and released at high Ca 2+ levels inside the nucleus [16]. Polymorphism in 3'UTR in the NCALD gene affects the mRNA stability and results in susceptibility to diabetic nephropathy [17].…”