Point mutations within 663-666 bp of intron 6 of the human TDO2 gene, associated with a number of psychiatric disorders, damage the YY-1 transcription factor binding site

FEBS Lett. 1999 Nov 26;462(1-2):85-8. doi: 10.1016/s0014-5793(99)01513-6.

Abstract

Single base mutations G-->A at position 663 and G-->T at position 666 of intron 6 of the human tryptophan oxygenase gene (TDO2) are associated with a variety of psychiatric disorders [Comings, D.E. et al. (1996) Pharmacogenetics 6, 307-318]. Binding of rat liver nuclear extract proteins to synthetic double-strand oligonucleotides corresponding to three allelic states of the region between 651 bp and 680 bp of human TDO2 intron 6 has been studied by gel shift assay. It has been demonstrated that to each allelic state of the region there corresponds a specific set of proteins that interacts with it. With the aid of computer analysis and using specific anti-YY-1 antibodies it has been shown that both mutations damage the YY-1 transcription factor binding site.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • DNA Damage
  • DNA-Binding Proteins / metabolism*
  • Erythroid-Specific DNA-Binding Factors
  • Humans
  • Introns
  • Mental Disorders / enzymology
  • Mental Disorders / genetics*
  • Point Mutation
  • Rats
  • Transcription Factors / metabolism*
  • Tryptophan Oxygenase / genetics*
  • Tryptophan Oxygenase / metabolism

Substances

  • DNA-Binding Proteins
  • Erythroid-Specific DNA-Binding Factors
  • Transcription Factors
  • Tryptophan Oxygenase