DREAM is a Ca2+-regulated transcriptional repressor

• Published in: Nature (London) 1999-03, Vol.398 (6722), p.80-84
• Main Authors: Carrión, Angel M., Link, Wolfgang A., Ledo, Fran, Mellström, Britt, Naranjo, Jose R.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Binding Sites; Calcium; Calcium - metabolism; Calcium-Binding Proteins - chemistry; Calcium-Binding Proteins - genetics; Calcium-Binding Proteins - physiology; Cell Line; Cellular biology; Deoxyribonucleic acid; DNA; DNA - metabolism; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - genetics; DNA-Binding Proteins - physiology; Enkephalins - genetics; Gene Expression Regulation; Genes; Genes, fos; Humanities and Social Sciences; Humans; Ions; Kv Channel-Interacting Proteins; letter; Molecular Sequence Data; multidisciplinary; Promoter Regions, Genetic; Protein Binding; Protein Precursors - genetics; Proteins; Repressor Proteins - chemistry; Repressor Proteins - genetics; Repressor Proteins - physiology; Science; Science (multidisciplinary); Sequence Homology, Amino Acid; Transcription, Genetic; Transfection
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/18044

Fluxes in amounts of intracellular calcium ions are important determinants of gene expression 1 , 2 , 3 . So far, Ca 2+ -regulated kinases and phosphatases have been implicated in changing the phosphorylation status of key transcription factors and thereby modulating their function 4 , 5 . In addition, direct effectors of Ca 2+ -induced gene expression have been suggested to exist in the nucleus 2 , although no such effectors have been identified yet. Expression of the human prodynorphin gene, which is involved inmemory acquisition and pain 6 , 7 , is regulated through its downstream regulatory element (DRE) sequence, which acts as a location-dependent gene silencer 8 . Here we isolate a new transcriptional repressor, DRE-antagonist modulator (DREAM), which specifically binds to the DRE. DREAM contains four Ca 2+ -binding domains of the EF-hand type. Upon stimulation by Ca 2+ , DREAM's ability to bind to the DRE and its repressor function are prevented. Mutation of the EF-hands abolishes the response of DREAM to Ca 2+ . In addition to the prodynorphin promoter, DREAM represses transcription from the early response gene c- fos . Thus, DREAM represents the first known Ca 2+ -binding protein to function as a DNA-binding transcriptional regulator.