The transcriptional repressor dream regulates Ca2+ homeostasis and viability in granule cerebellar neurons

The structure of the human NCX3 gene is known and specific enhancers for both muscle and neuronal expression as well as a cAMP response element (CRE) have been identified in the proximal promoter. A direct mechanism for the regulation of gene expression involves the protein DREAM (Downstream Regulatory Element Antagonist Modulator), which has been found to bind to specific DRE sites to repress transcription of several genes. Binding of calcium to DREAM through EF-hand motifs reduces its affinity for DNA, leading to derepression of target genes. We have identified a doublet of DRE sites in the 5' -untranslated region of the NCX3 gene that mediates its repression by DREAM in the cerebellum of transgenic mice . Overexpression of EFmDREAMin hippocampus and cerebellum of transgenic mice significantly reduced NCX3 mRNA and protein levels. Thus, the downregulation of the regulator of calcium homeostasis NCX3 by calcium-regulated DREAM is a striking example of the autoregulatory property of the calcium signal in neurons.