Deletion of the RUNX1 binding site in the erythroid cell‐specific regulatory element of the ABO gene in two individuals with the Am phenotype. Issue 2 (2nd September 2013)

• Record Type: Journal Article
• Authors: Takahashi, Y.; Isa, K.; Sano, R.; Nakajima, T.; Kubo, R.; Takahashi, K.; Kominato, Y.; Tsuneyama, H.; Ogasawara, K.; Uchikawa, M.
• Is Part Of: Vox sanguinis. Volume 106:Issue 2(2014)
• Page Start: 167
• Page End: 175
• Publication Date: 2013-09-02
• Subjects: Blood -- Periodicals; Blood -- Transfusion -- Periodicals; Immunohematology -- Periodicals; Immunopathology -- Periodicals; 615.39
• DOI: 10.1111/vox.12077
• Languages: English
• ISSNs: 0042-9007

Abstract

<abstract abstract-type="main" id="vox12077-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="vox12077-sec-0001" sec-type="section"> <title>Background and Objectives</title> <p>An erythroid cell‐specific regulatory element, referred to as the +5·8‐kb site, had been identified in the first intron of the human <italic>ABO</italic> blood group gene. Subsequent studies revealed that either a 5·8‐kb deletion including the +5·8‐kb site or disruption of a GATA factor binding motif at the site was present in all B<sub>m</sub> and AB<sub>m</sub> individuals examined. We investigated the molecular mechanism of the A<sub>m</sub> phenotype, which is analogous to the B<sub>m</sub> phenotype.</p> </sec> <sec id="vox12077-sec-0002" sec-type="section"> <title>Materials and Methods</title> <p>Genomic DNAs were prepared from peripheral blood of two A<sub>m</sub> individuals, and the nucleotide sequences were investigated using PCR and direct sequencing. Electrophoretic mobility shift assay (EMSA) and promoter assay with K562 cells were carried out.</p> </sec> <sec id="vox12077-sec-0003" sec-type="section"> <title>Results</title> <p>A novel 23‐bp nucleotide deletion was found at the +5·8‐kb site in both individuals. EMSAs demonstrated binding of the transcription factor RUNX1 to the nucleotides within the deletion. Promoter assays showed that the deletion reduced the transcriptional activity of the +5·8‐kb site.</p> </sec> <sec id="vox12077-sec-0004" sec-type="section"> <title>Conclusion</title> <p>Deletion of the 23‐bp nucleotides including the RUNX1 binding site decreases transcription of the <italic>A</italic> allele, resulting in the reduction in A antigen expression in the A<sub>m</sub> phenotype.</p> </sec> </abstract>