BackgroundThe human ABO blood group system is important in transfusion and organ transplantation. Although the molecular basis of the ABO gene has been established, recent studies have begun to characterize the mechanism of the ABO gene expression.Materials and MethodsTransient transfection assays were carried out in human erythroleukaemia HEL cells and human gastric cancer KATOIII cells. Electrophoretic mobility shift assays were performed using nuclear extracts derived from both cells.ResultsOur characterization of the 5′‐upstream sequence of the ABO genes indicated that the region between −117 and +31 is essential to direct expression of a reporter gene in erythroid cells. We show that a sequence located between positions −22 and −14 of the ABO promoter binds a ubiquitous transcription factor Sp1 or Sp1‐like protein(s). Mutation of this site abrogates binding of those factors and reduces the ability of the ABO promoter to function in erythroleukaemia cells and gastric cancer cells.ConclusionThe 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.