Disruption of a GATA motif in the Duffy gene promoter abolishes erythroid gene expression in Duffy-negative individuals

Nat Genet. 1995 Jun;10(2):224-8. doi: 10.1038/ng0695-224.

Abstract

The mRNA for the Duffy blood group antigen, the erythrocyte receptor for the Plasmodium vivax malaria parasite, has recently been cloned and shown to encode a widely expressed chemokine receptor. Here, we show that the Duffy antigen/chemokine receptor gene (DARC) is composed of a single exon and that most Duffy-negative blacks carry a silent FY*B allele with a single T to C substitution at nucleotide -46. This mutation impairs the promoter activity in erythroid cells by disrupting a binding site for the GATA1 erythroid transcription factor. With the recent characterization of the FY*A and FY*B alleles, these findings provide the molecular basis of the Duffy blood group system and an explanation for the erythroid-specific repression of the DARC gene in Duffy-negative individuals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Protozoan*
  • Base Sequence
  • Black People / genetics
  • Carrier Proteins / genetics
  • Chromosome Mapping
  • DNA-Binding Proteins / genetics*
  • Duffy Blood-Group System / genetics*
  • Erythrocytes / chemistry*
  • Erythroid-Specific DNA-Binding Factors
  • GATA1 Transcription Factor
  • Gene Expression
  • Genotype
  • Humans
  • Molecular Sequence Data
  • Mutation
  • Promoter Regions, Genetic*
  • Protozoan Proteins / genetics
  • Receptors, Cell Surface / genetics
  • Transcription Factors / genetics*
  • Transcription, Genetic
  • Tumor Cells, Cultured

Substances

  • ACKR1 protein, human
  • Antigens, Protozoan
  • Carrier Proteins
  • DNA-Binding Proteins
  • Duffy Blood-Group System
  • Duffy antigen binding protein, Plasmodium
  • Erythroid-Specific DNA-Binding Factors
  • GATA1 Transcription Factor
  • GATA1 protein, human
  • Protozoan Proteins
  • Receptors, Cell Surface
  • Transcription Factors

Associated data

  • GENBANK/X85785