Futscher Bernard W, Oshiro Marc M, Wozniak Ryan J, Holtan Nicholas, Hanigan Christin L, Duan Hong, Domann Frederick E
Department of Pharmacology and Toxicology, Bone Marrow Transplant Program, Arizona Cancer Center, The University of Arizona, Tucson, Arizona 85724, USA.
Nat Genet. 2002 Jun;31(2):175-9. doi: 10.1038/ng886. Epub 2002 May 20.
The nucleotide 5-methylcytosine is involved in processes crucial in mammalian development, such as X-chromosome inactivation and gene imprinting. 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; however, it has been difficult to identify clear examples of such genes, particularly in humans. 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.
核苷酸5-甲基胞嘧啶参与哺乳动物发育过程中的关键进程，如X染色体失活和基因印记。此外，长期以来人们一直推测胞嘧啶甲基化参与发育调控基因的细胞类型特异性表达的建立和维持；然而，很难找到此类基因的明确实例，尤其是在人类中。在此我们提供证据表明，丝氨酸蛋白酶抑制剂B5基因（SERPINB5）启动子的胞嘧啶甲基化部分控制着SERPINB5正常的细胞类型特异性表达。在表达SERPINB5的正常细胞中，SERPINB5启动子未甲基化，启动子区域具有乙酰化组蛋白和可及的染色质结构。相比之下，不表达SERPINB5的正常细胞具有完全甲基化的SERPINB5启动子，组蛋白低乙酰化，染色质结构不可及，并且转录抑制可通过DNA甲基化抑制得以缓解。这些发现表明，胞嘧啶甲基化在细胞类型受限的基因表达的建立和维持中很重要。
