title: Characterization of the Duffy gene promoter: evidence for tissue-specific abolishment of expression in Fy(a-b-) of black individuals.
abstract: We have previously identified a novel first exon of Duffy gene and two inverse GATA motifs in the 600 bp 5' flanking region. The proximal GATA is positioned downstream from the start position of endothelium and upstream from that of erythroid. One base substitution (-365T --> C) was found in the proximal GATA motif from three black Fy(a-b-) individuals, and was regarded as a common polymorphic mutation in black Fy(a-b-) individuals. The upstream sequence of the novel first exon was inserted in the upstream of chloramphenicol acetyltransferase (CAT) gene and transfected in human erythroleukemia cell line (HEL) and human microvascular endothelial cells (HMvEC). The black type mutation abolished the CAT transcription in HEL cells but not in HMvEC. Deletion mutagenesis study revealed that the proximal GATA motif represent the erythroid regulatory core region for Duffy gene. Gel shift assay showed that the proximal GATA motif is the target sequence of GATA-1. These studies indicate that the black type mutation abolishes Duffy gene expression in erythroid but not in postcapillary venule endothelium, which is compatible with the Northern blot and immunohistochemical observation in black Fy(a-b-) individuals.
authors.affiliation: Department of Legal Medicine and Human Genetics, Jichi Medical School, Tochigi, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Iwamoto
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: N
authors.initials: N
authors.lastname: Sugimoto
authors.forename: H
authors.initials: H
authors.lastname: Okuda
authors.forename: E
authors.initials: E
authors.lastname: Kajii
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D044383:Black People / Q000235:genetics*; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000378:metabolism; D004375:Duffy Blood-Group System / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D014018:Tissue Distribution; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; D004375:Duffy Blood-Group System; D014157:Transcription Factors