DREAM regulates insulin promoter activity through newly identified DRE element

• Published in: Central European journal of biology 2013-02, Vol.8 (2), p.97-106
• Main Authors: Daneva, Teodora, Pashova, Shina, Emilova, Radoslava, Padeshki, Plamen, Gagov, Hristo, Georgiev, Volodia
• Format: Article
• Language: English
• Subjects: antagonists; Biochemistry; Biomedical and Life Sciences; Biotechnology; calcium; Cell Biology; DREAM; Gene transcription; genes; Human Genetics; humans; Immunology; Insulin; Islets of Langerhans; Life Sciences; Promoter activity; proteins; Research Article; transcription (genetics)
• ISSN: 1895-104X; 2391-5412; 1644-3632; 2391-5412
• DOI: 10.2478/s11535-013-0123-3

Downstream regulatory element antagonist modulator (DREAM) protein is a 31 kDa Ca²⁺-regulated transcriptional repressor. It functions as a silencer of the gene transcription. In low intracellular free Ca²⁺ concentration DREAM tightly binds to the downstream regulatory element (DRE) of gene promoter and impedes the transcription. In higher Ca²⁺ concentrations DREAM binds Ca²⁺ 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 Ca²⁺-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.