Agger Karl, Christensen Jesper, Cloos Paul A C, Helin Kristian
Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen, Denmark.
Curr Opin Genet Dev. 2008 Apr;18(2):159-68. doi: 10.1016/j.gde.2007.12.003. Epub 2008 Feb 20.
Epigenetic information refers to heritable changes in gene function that are stable between cell divisions but which is not a result of changes in the DNA sequence. Part of the epigenetic mechanism has been ascribed to modifications of histones or DNA that affects the transcription of specific genes. In this context, post-translational modifications of histone tails, in particular methylation of lysines, are regarded as important for the storage of epigenetic information. Regulation of this information plays an important role during cellular differentiation where cells with different characteristic features evolve from the same ancestor, despite identical genomic material. The characterization of several enzymes catalyzing histone lysine methylation have supported this concept by showing the requirement of these enzymes for normal development and their involvement in diseases such as cancer. The recent identification of proteins with histone demethylase activity has shown that the methylated mark is much more dynamic than previously anticipated, thereby potentially challenging the concept of histone-methylation in stable epigenetic programming.
表观遗传信息是指基因功能上可遗传的变化，这些变化在细胞分裂之间是稳定的，但并非DNA序列变化的结果。部分表观遗传机制归因于影响特定基因转录的组蛋白或DNA修饰。在此背景下，组蛋白尾部的翻译后修饰，尤其是赖氨酸的甲基化，被认为对表观遗传信息的存储很重要。在细胞分化过程中，尽管基因组物质相同，但具有不同特征的细胞从同一祖先进化而来，这种信息的调控起着重要作用。几种催化组蛋白赖氨酸甲基化的酶的特性研究支持了这一概念，表明这些酶对正常发育是必需的，且参与诸如癌症等疾病。最近对具有组蛋白去甲基化酶活性的蛋白质的鉴定表明，甲基化标记比之前预期的更具动态性，从而可能对稳定表观遗传编程中组蛋白甲基化的概念提出挑战。
