title: Disruption of a GATA motif in the Duffy gene promoter abolishes erythroid gene expression in Duffy-negative individuals.
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.
authors.affiliation: Unité INSERM U76, GIP-Institut National de la Transfusion Sanguine, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Tournamille
authors.forename: Y
authors.initials: Y
authors.lastname: Colin
authors.forename: J P
authors.initials: JP
authors.lastname: Cartron
authors.forename: C
authors.initials: C
authors.lastname: Le Van Kim
mesh_terms: D000953:Antigens, Protozoan; D001483:Base Sequence; D044383:Black People / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D002874:Chromosome Mapping; D004268:DNA-Binding Proteins / Q000235:genetics*; D004375:Duffy Blood-Group System / Q000235:genetics*; D004912:Erythrocytes / Q000737:chemistry*; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic; D015800:Protozoan Proteins / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
chemical_list: C473745:ACKR1 protein, human; D000953:Antigens, Protozoan; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D004375:Duffy Blood-Group System; C066001:Duffy antigen binding protein, Plasmodium; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface; D014157:Transcription Factors