Expression of human histo-blood group ABO genes is dependent upon DNA methylation of the promoter region

被引：80

作者：

Kominato, Y

Hata, Y

Takizawa, H

Tsuchiya, T

Tsukada, J

Yamamoto, F

机构：

[1] Toyama Med & Pharmaceut Univ, Fac Med, Dept Legal Med, Toyama 9300194, Japan

[2] Tokyo Med & Dent Univ, Med Res Inst, Tokyo 1130034, Japan

[3] Univ Occupat & Environm Hlth, Sch Med, Kitakyushu, Fukuoka 8070804, Japan

[4] Univ Occupat & Environm Hlth, Sch Hlth Sci, Dept Internal Med 1, Kitakyushu, Fukuoka 8070804, Japan

[5] Burnham Inst, La Jolla, CA 92037 USA

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 1999年 / 274卷 / 52期

关键词：

D O I：

10.1074/jbc.274.52.37240

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：37240 / 37250

页数：11

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