Ballestar Esteban, Esteller Manel
Cancer Epigenetics Laboratory, Spanish National Cancer Centre, Madrid, Spain.
Biochem Cell Biol. 2005 Jun;83(3):374-84. doi: 10.1139/o05-035.
In recent years, epigenetic alterations have come to prominence in cancer research. In particular, hypermethylation of CpG islands located in the promoter regions of tumor-suppressor genes is now firmly established as an important mechanism for gene inactivation in cancer. One of the most remarkable achievements in the field has been the identification of the methyl-CpG-binding domain family of proteins, which provide mechanistic links between specific patterns of DNA methylation and histone modifications. Although many of the current data indicate that methyl-CpG-binding proteins play a key role in maintaining a transcriptionally inactive state of methylated genes, MBD4 is also known to be involved in excision repair of T:G mismatches. The latter is a member of this family of proteins and appears to play a role in reducing mutations at 5-methylcytosine. This review examines the contribution of methyl-CpG-binding proteins in the epigenetic pathway of cancer.
近年来，表观遗传改变在癌症研究中备受关注。特别是，位于肿瘤抑制基因启动子区域的CpG岛的高甲基化现已被确认为癌症中基因失活的重要机制。该领域最显著的成就之一是鉴定出甲基-CpG结合结构域蛋白家族，它们在特定的DNA甲基化模式和组蛋白修饰之间提供了机制联系。尽管目前的许多数据表明甲基-CpG结合蛋白在维持甲基化基因的转录失活状态中起关键作用，但MBD4也被认为参与T:G错配的切除修复。后者是该蛋白家族的成员，似乎在减少5-甲基胞嘧啶处的突变中发挥作用。本文综述了甲基-CpG结合蛋白在癌症表观遗传途径中的作用。
