Lu S, Davies P J
Department of Pharmacology, University of Texas Medical School, Houston, TX 77225, USA.
Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4692-7. doi: 10.1073/pnas.94.9.4692.
We have investigated the role of DNA methylation in the regulation of the expression of the human tissue transglutaminase gene. Studies on the methylation of the transglutaminase promoter in normal and neoplastic human cells demonstrated that the promoter is methylated in vivo and hypomethylation of the promoter is correlated with constitutive gene expression. Demethylation of the promoter in vivo by treatment of the cells with 5-azacytidine increased transglutaminase expression and hypermethylation of the promoter in vitro suppressed its activity. These studies suggest that alternations in DNA methylation may be one of the mechanisms regulating the tissue-specific expression of the tissue transglutaminase gene.
我们研究了DNA甲基化在人组织转谷氨酰胺酶基因表达调控中的作用。对正常和肿瘤人类细胞中转谷氨酰胺酶启动子甲基化的研究表明,该启动子在体内发生甲基化,且启动子的低甲基化与基因的组成型表达相关。用5-氮杂胞苷处理细胞使启动子在体内发生去甲基化,从而增加了转谷氨酰胺酶的表达,而启动子在体外的高甲基化则抑制了其活性。这些研究表明,DNA甲基化的改变可能是调节组织转谷氨酰胺酶基因组织特异性表达的机制之一。