Characterization of the human ABO gene promoter in erythroid cell lineage

Hata, Yukiko; Kominato, Yoshihiko; Yamamoto, Fumiichiro; Takizawa, Hisao

doi:10.1046/j.0042-9007.2001.00134.x

Cited by 39 publications

(63 citation statements)

References 25 publications

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“…However, a cell-type-specific promoter has been demonstrated at the 5Ј boundary of the CpG island, although its role remains obscure. Furthermore, 4 tandem copies of a 43-bp repeat unit located 3.8 kb upstream of transcription starting exon 1 driven by the proximal promoter have been shown to have enhancer activity in human gastric cancer KATOIII cells, but not in human erythroleukemia HEL cells, 11,14 suggesting that the enhancer potential of this element is dependent on cell type. Recently, genomewide approaches for the discovery of enhancers have become available.…”

Section: Introductionmentioning

confidence: 99%

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Expression of ABO blood-group genes is dependent upon an erythroid cell–specific regulatory element that is deleted in persons with the Bm phenotype

Sano

Nakajima

Takahashi

et al. 2012

Blood

126

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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 cellspecific manner. Electrophoretic mobilityshift 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.

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Section: Introductionmentioning

confidence: 99%

“…Studies of the human ABO gene using cultured cells have demonstrated transcriptional regulatory elements. [11][12][13][14][15][16][17] A proximal promoter and a negative regulatory region just upstream from it have been found within the ABO CpG island. The proximal promoter is rich in CpG and shows no apparent tissue specificity.…”

Section: Introductionmentioning

confidence: 99%

Expression of ABO blood-group genes is dependent upon an erythroid cell–specific regulatory element that is deleted in persons with the Bm phenotype

Sano

Nakajima

Takahashi

et al. 2012

Blood

126

View full text Add to dashboard Cite

show abstract

“…A proximal promoter has been found within the ABO CpG island (CGI) (9,10). However, a cell type-specific, distal promoter has been demonstrated at the 5Ј boundary of the CGI, although the amount of transcript from this promoter was very small (3).…”

mentioning

confidence: 99%

Epithelial Expression of Human ABO Blood Group Genes Is Dependent upon a Downstream Regulatory Element Functioning through an Epithelial Cell-specific Transcription Factor, Elf5

Sano

Nakajima

Takahashi

et al. 2016

Journal of Biological Chemistry

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The human ABO blood group system is of great importance in blood transfusion and organ transplantation. The ABO system is composed of complex carbohydrate structures that are biosynthesized by A-and B-transferases encoded by the ABO gene. However, the mechanisms regulating ABO gene expression in epithelial cells remain obscure. On the basis of DNase I-hypersensitive sites in and around ABO in epithelial cells, we prepared reporter plasmid constructs including these sites. Subsequent luciferase assays and histone modifications indicated a novel positive regulatory element, designated the ؉22.6-kb site, downstream from ABO, and this was shown to enhance ABO promoter activity in an epithelial cell-specific manner. Expression of ABO and B-antigen was reduced in gastric cancer KATOIII cells by biallelic deletion of the ؉22.6-kb site using the CRISPR/Cas9 system. Electrophoretic mobility shift assay and chromatin immunoprecipitation assay demonstrated that the site bound to an epithelial cell-specific transcription factor, Elf5. Mutation of the Ets binding motifs to abrogate binding of this factor reduced the regulatory activity of the ؉22.6-kb site. Furthermore, ELF5 knockdown with shRNA reduced both endogenous transcription from ABO and B-antigen expression in KATOIII cells. Thus, Elf5 appeared to be involved in the enhancer potential of the ؉22.6-kb site. These results support the contention that ABO expression is dependent upon a downstream positive regulatory element functioning through a tissue-restricted transcription factor, Elf5, in epithelial cells.The human ABO blood group system is of great importance in blood transfusion and organ transplantation. The system comprises complex carbohydrate structures that are biosynthesized by the A-and B-transferases encoded by the A and B genes, respectively (1). The ABO genes consist of seven exons spanning more than 20 kb of genomic DNA, and two critical single-base substitutions in the last coding exon result in amino acid substitutions responsible for the difference in donor nucleotide sugar substrate specificity between A-and B-transferases (2). A single base deletion in exon 6 has been ascribed to a shift in the reading frame of codons and abolition of A-transferase activity in most O alleles. On the other hand, the distribution of the A-and B-antigens is cell type-specific; for example, the antigens are expressed on red blood cells and epithelial cells, as well as in salivary glands, although they are absent from the central nervous system, muscle, and connective tissue. Moreover, ABH antigens are known to be expressed during the maturation of erythroid and epithelial cells; for example, when erythroid cells differentiate in vitro, ABO is expressed at an undetectable level in the early phase, increases subsequently, and then decreases later (3, 4). In addition to the normal cell differentiation process, changes in ABH antigen expression have also been documented in abnormal processes such as tumorigenesis (1). Reduction or complete deletion of A/B antigen expressi...

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“…The association between the ABO blood groups and various diseases has been a subject of great interest, 8 and approximately 70 such associations have been identified. 1 -3,5 The ABO antigens are glycol proteins found throughout the body, possibly even in bone tissue, which suggests that there might be a biological connection between ABO blood groups and osteoporosis.…”

Section: B-b Lu K-h LI Abo Blood Groups and Osteoporosis Severitymentioning

confidence: 99%

“…4 The activation of the ABO promoter appears to be influenced by the binding of Sp1 or Sp1-like protein(s) in both erythroid and epithelial cell lineages. 8 Osteoporosis is a common disease with a strong genetic component, which is characterized by low bone mass, microarchitectural deterioration of the bone tissue and an increased risk of fracture. 11 Twin and family studies have shown that genetic factors play an important role in regulating BMD.…”

Section: B-b Lu K-h LI Abo Blood Groups and Osteoporosis Severitymentioning

confidence: 99%

Association between ABO Blood Groups and Osteoporosis Severity in Chinese Adults Aged 50 Years and over

2011

J Int Med Res

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This study investigated whether the ABO blood groups contributed to the severity of osteoporosis in 1452 community-dwelling Chinese adults aged 50 -85 years. Osteoporosis severity was scored as: F 0 , no osteoporosis; F 1 , osteopenia; F 2 , osteoporosis; and F 3 , severe osteoporosis. The proportions of adults with a non-O blood group were 55.0%, 62.0%, 70.8% and 72.6% for the groups with F 0 , F 1 , F 2 and F 3 osteoporosis scores, respectively. Having a non-O blood group was associated with an increased severity of osteoporosis, even after adjustment for gender, age and cigarette consumption (odds ratio 1.8; 95% confidence interval 1.0, 2.9). This study demonstrated that having a non-O blood group was an independent risk factor for the progression of osteoporosis in Chinese adults with osteoporosis aged ≥ 50 years.

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Characterization of the human ABO gene promoter in erythroid cell lineage

Abstract: The expression of the ABO promoter appears to be influenced by the binding of Sp1 or Sp1-like protein(s) in both erythroid and epithelial cell lineages.

Cited by 39 publications

References 25 publications

Expression of ABO blood-group genes is dependent upon an erythroid cell–specific regulatory element that is deleted in persons with the Bm phenotype

Expression of ABO blood-group genes is dependent upon an erythroid cell–specific regulatory element that is deleted in persons with the Bm phenotype

Epithelial Expression of Human ABO Blood Group Genes Is Dependent upon a Downstream Regulatory Element Functioning through an Epithelial Cell-specific Transcription Factor, Elf5

Association between ABO Blood Groups and Osteoporosis Severity in Chinese Adults Aged 50 Years and over

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