title: Expression of ABO blood-group genes is dependent upon an erythroid cell-specific regulatory element that is deleted in persons with the B(m) phenotype.
abstract: The ABO blood group is of great importance in blood transfusion and organ transplantation. However, the mechanisms regulating human ABO gene expression remain obscure. On the basis of DNase I-hypersensitive sites in and upstream of ABO in K562 cells, in the present study, we prepared reporter plasmid constructs including these sites. Subsequent luciferase assays indicated a novel positive regulatory element in intron 1. This element was shown to enhance ABO promoter activity in an erythroid cell-specific manner. Electrophoretic mobility-shift assays demonstrated that it bound to the tissue-restricted transcription factor GATA-1. Mutation of the GATA motifs to abrogate binding of this factor reduced the regulatory activity of the element. Therefore, GATA-1 appears to be involved in the cell-specific activity of the element. Furthermore, we found that a partial deletion in intron 1 involving the element was associated with B(m) phenotypes. Therefore, it is plausible that deletion of the erythroid cell-specific regulatory element could down-regulate transcription in the B(m) allele, leading to reduction of B-antigen expression in cells of erythroid lineage, but not in mucus-secreting cells. These results support the contention that the enhancer-like element in intron 1 of ABO has a significant function in erythroid cells.
authors.affiliation: Department of Legal Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Sano
authors.forename: Tamiko
authors.initials: T
authors.lastname: Nakajima
authors.forename: Keiko
authors.initials: K
authors.lastname: Takahashi
authors.forename: Rieko
authors.initials: R
authors.lastname: Kubo
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Kominato
authors.forename: Junichi
authors.initials: J
authors.lastname: Tsukada
authors.forename: Haruo
authors.initials: H
authors.lastname: Takeshita
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Yasuda
authors.forename: Kazuto
authors.initials: K
authors.lastname: Ito
authors.forename: Takayuki
authors.initials: T
authors.lastname: Maruhashi
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yokohama
authors.forename: Kazumi
authors.initials: K
authors.lastname: Isa
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ogasawara
authors.forename: Makoto
authors.initials: M
authors.lastname: Uchikawa
mesh_terms: D000017:ABO Blood-Group System / Q000096:biosynthesis* / Q000235:genetics; D000483:Alleles; D004742:Enhancer Elements, Genetic / Q000502:physiology*; D041905:Erythroid Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D050982:GATA1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007438:Introns / Q000502:physiology*; D020014:K562 Cells; D008297:Male; D010641:Phenotype; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D000017:ABO Blood-Group System; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human