Novel dual repressor elements for neuronal cell-specific transcription of the rat 5-HT1A receptor gene

J Biol Chem. 2000 Mar 17;275(11):8161-8. doi: 10.1074/jbc.275.11.8161.


The level of expression of the 5-HT1A receptor in the raphe and limbic systems is implicated in the etiology and treatment of major depression and anxiety disorders. The rat 5-HT1A receptor gene is regulated by a proximal TATA-driven promoter and by upstream repressors that inhibit gene expression. Deletion of a 71-base pair (bp) segment between -1590/-1519 bp of the 5-HT1A receptor gene induced over 10-fold enhancement of transcriptional activity in both 5-HT1A receptor-expressing (RN46A raphe and SN48 septal) cells and receptor-negative (L6 myoblast and C6 glioma) cells. A 31-bp segment of the repressor was protected from DNase I digestion by RN46A or L6 nuclear extracts. Within the 31-bp segment, a single protein complex was present in receptor-expressing cells that bound a novel 14-bp DNA element; in receptor-negative cells, an additional complex bound an adjacent 12-bp sequence. In receptor-positive but not receptor-negative cells, mutation of the 14-bp element to eliminate protein binding abrogated repression to nearly the same extent as deletion of the -1590/-1519 bp segment. Additional mutation of both 14-bp and 12-bp elements abolished protein binding and repressor activity in receptor-negative cells. Thus a single protein-DNA complex at the 14-bp element represses the 5-HT1A receptor gene in 5-HT1A receptor-positive neuronal cells, whereas adjacent DNA elements provide a dual repression mechanism in 5-HT1A receptor-negative cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety Disorders / etiology
  • DNA-Binding Proteins / metabolism
  • Depressive Disorder / etiology
  • Enhancer Elements, Genetic
  • Gene Expression Regulation
  • Molecular Sequence Data
  • Neurons / metabolism*
  • Promoter Regions, Genetic
  • Protein Binding
  • Raphe Nuclei / cytology
  • Raphe Nuclei / metabolism*
  • Rats
  • Receptors, Serotonin / biosynthesis
  • Receptors, Serotonin / genetics*
  • Receptors, Serotonin, 5-HT1
  • Regulatory Sequences, Nucleic Acid*
  • Septum of Brain / cytology
  • Septum of Brain / metabolism
  • Transcription, Genetic


  • DNA-Binding Proteins
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1

Associated data

  • GENBANK/AF217200