Expression of human histo-blood group ABO genes is dependent upon DNA methylation of the promoter region
Expression of human histo-blood group ABO genes is dependent upon DNA methylation of the promoter region
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DOI：
10.1074/jbc.274.52.37240
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发表时间：
1999-12-24
影响因子：
4.8
通讯作者：
Yamamoto, F
中科院分区：
文献类型：
--
作者：
Kominato, Y;Hata, Y;Yamamoto, F
我们研究了DNA甲基化在人类组织血型ABO基因表达中的调节作用。ABO基因启动子区含有一个CpG岛，其甲基化状态与检测细胞系中的基因表达密切相关。CPG岛被发现低甲基化的一些细胞系，表达ABO基因，而其他细胞系，不表达ABO基因是高甲基化。而ABO基因启动子的组成性转录活性在表达和非表达细胞系中通过瞬时转染含有ABO基因启动子序列的报告构建体证明，HhaI甲基化酶催化的启动子区域的体外甲基化在DNA转染前抑制了启动子活性，当引入表达胃癌细胞系KATOIII细胞中时。另一方面，在非表达胃癌细胞系MKN 28细胞中，用DNA甲基转移酶抑制剂5-氮杂-2 '-脱氧胞苷处理导致ABO：基因启动子的去甲基化和A-转移酶信息的出现，以及由A-转移酶合成的A-抗原。综上所述，这些研究表明，ABO基因启动子的DNA甲基化可能在ABO基因表达调控中起重要作用。
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.