Expression of human histo-blood group ABO genes is dependent upon DNA methylation of the promoter region.
We have investigated the regulatory role of DNA methylation in the expression of the human histo-blood group ABO genes. The ABO gene promoter region contains a CpG island whose methylation status correlates well with gene expression in the cell lines tested. The CpG island was found hypomethylated in some cell lines that expressed ABO genes, whereas the other cell lines that did not express ABO genes were hypermethylated. Whereas constitutive transcriptional activity of the ABO gene promoter was demonstrated in both expressor and nonexpressor cell lines by transient transfection of reporter constructs containing the ABO gene promoter sequence, HhaI methylase-catalyzed in vitro methylation of the promoter region prior to DNA transfection suppressed the promoter activity when introduced into the expressor gastric cancer cell line KATOIII cells. On the other hand, in the nonexpressor gastric cancer cell line MKN28 cells, treatment with DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine resulted in demethylation of the ABO gene promoter and appearance of A-transferase messages, as well as A-antigens synthesized by A-transferase. Taken together, these studies suggest that DNA methylation of the ABO gene promoter may play an important role in the regulation of ABO gene expression.
Kominato
Y
Y
Toyama Medical and Pharmaceutical University, Faculty of Medicine, Department of Legal Medicine, Toyama 930-0194, Japan. ykomilm@ms.toyama-mpu.ac.jp
Hata
Y
Y
Takizawa
H
H
Tsuchiya
T
T
Tsukada
J
J
Yamamoto
F
F
D000017:ABO Blood-Group System / Q000235:genetics*; D001483:Base Sequence; D019175:DNA Methylation; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D014407:Tumor Cells, Cultured
D000017:ABO Blood-Group System