Role for DNA methylation in the control of cell type-specific maspin expression
Role for DNA methylation in the control of cell type-specific maspin expression
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DOI：
10.1038/ng886
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发表时间：
2002-06-01
期刊：
影响因子：
30.8
通讯作者：
Domann, FE
中科院分区：
文献类型：
--
作者：
Futscher, BW;Oshiro, MM;Domann, FE
核苷酸5-甲基胞嘧啶参与哺乳动物发育的关键过程，如X染色体失活和基因印记（1-5）。此外，胞嘧啶甲基化长期以来一直被推测参与发育调控基因的细胞类型特异性表达的建立和维持6，7;然而，很难确定这些基因的明确例子，特别是在人类中（8）。在这里，我们提供的证据表明，胞嘧啶甲基化的maspin基因（SERPINB 5）启动子控制，部分，正常细胞类型特异性SERPINB 5的表达。在表达SERPINB 5的正常细胞中，SERPINB 5启动子是未甲基化的，并且启动子区域具有乙酰化的组蛋白和可接近的染色质结构。相比之下，不表达SERPINB 5的正常细胞具有完全甲基化的SERPINB 5启动子和低乙酰化的组蛋白，不可接近的染色质结构和通过抑制DNA甲基化而缓解的转录抑制。这些发现表明胞嘧啶甲基化在细胞类型限制性基因表达的建立和维持中是重要的。
The nucleotide 5-methylcytosine is involved in processes crucial in mammalian development, such as X-chromosome inactivation and gene imprinting(1-5). In addition, cytosine methylation has long been speculated to be involved in the establishment and maintenance of cell type specific expression of developmentally regulated genes 6,7; however, it has been difficult to identify clear examples of such genes, particularly in humans(8). Here we provide evidence that cytosine methylation of the maspin gene (SERPINB5) promoter controls, in part, normal cell type specific SERPINB5 expression. In normal cells expressing SERPINB5, the SERPINB5 promoter is unmethylated and the promoter region has acetylated histones and an accessible chromatin structure. By contrast, normal cells that do not express SERPINB5 have a completely methylated SERPINB5 promoter with hypoacetylated histones, an inaccessible chromatin structure and a transcriptional repression that is relieved by inhibition of DNA methylation. These findings indicate that cytosine methylation is important in the establishment and maintenance of cell type restricted gene expression.