DREAM is a Ca2+-regulated transcriptional repressor

Nature. 1999 Mar 4;398(6722):80-4. doi: 10.1038/18044.


Fluxes in amounts of intracellular calcium ions are important determinants of gene expression. So far, Ca2+-regulated kinases and phosphatases have been implicated in changing the phosphorylation status of key transcription factors and thereby modulating their function. In addition, direct effectors of Ca2+-induced gene expression have been suggested to exist in the nucleus, although no such effectors have been identified yet. Expression of the human prodynorphin gene, which is involved in memory acquisition and pain, is regulated through its downstream regulatory element (DRE) sequence, which acts as a location-dependent gene silencer. Here we isolate a new transcriptional repressor, DRE-antagonist modulator (DREAM), which specifically binds to the DRE. DREAM contains four Ca2+-binding domains of the EF-hand type. Upon stimulation by Ca2+, 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 Ca2+. In addition to the prodynorphin promoter, DREAM represses transcription from the early response gene c-fos. Thus, DREAM represents the first known Ca2+-binding protein to function as a DNA-binding transcriptional regulator.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Calcium / metabolism
  • Calcium-Binding Proteins / chemistry
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / physiology*
  • Cell Line
  • DNA / metabolism
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology
  • Enkephalins / genetics
  • Gene Expression Regulation*
  • Genes, fos
  • Humans
  • Kv Channel-Interacting Proteins
  • Molecular Sequence Data
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Precursors / genetics
  • Repressor Proteins / chemistry
  • Repressor Proteins / genetics
  • Repressor Proteins / physiology*
  • Sequence Homology, Amino Acid
  • Transcription, Genetic
  • Transfection


  • Calcium-Binding Proteins
  • DNA-Binding Proteins
  • Enkephalins
  • KCNIP3 protein, human
  • Kv Channel-Interacting Proteins
  • Protein Precursors
  • Repressor Proteins
  • DNA
  • preproenkephalin
  • Calcium

Associated data

  • GENBANK/AJ131730