Brero A, Leonhardt H, Cardoso M C
Max Delbrück Center for Molecular Medicine, FVK, Berlin, Germany.
Curr Top Microbiol Immunol. 2006;301:21-44. doi: 10.1007/3-540-31390-7_2.
Most cells in multicellular organisms contain identical genetic information but differ in their epigenetic information. The latter is encoded at the molecular level by post-replicative methylation of certain DNA bases (in mammals 5-methyl cytosine at CpG sites) and multiple histone modifications in chromatin. In addition, higher-order chromatin structures are generated during differentiation, which might impact on genome expression and stability. The epigenetic information needs to be "translated" in order to define specific cell types with specific sets of active and inactive genes, collectively called the epigenome. Once established, the epigenome needs to be "replicated" at each cell division cycle, i.e., both genetic and epigenetic information have to be faithfully duplicated, which implies a tight coordination between the DNA replication machinery and epigenetic regulators. In this review, we focus on the molecules and mechanisms responsible for the replication and translation of DNA methylation in mammals as one of the central epigenetic marks.
多细胞生物中的大多数细胞都包含相同的遗传信息,但它们的表观遗传信息却有所不同。后者在分子水平上由某些DNA碱基的复制后甲基化(在哺乳动物中为CpG位点的5-甲基胞嘧啶)以及染色质中的多种组蛋白修饰编码。此外,在分化过程中会产生更高阶的染色质结构,这可能会影响基因组的表达和稳定性。表观遗传信息需要被“翻译”,以便定义具有特定活性和非活性基因集的特定细胞类型,这些基因共同构成表观基因组。一旦建立,表观基因组需要在每个细胞分裂周期中被“复制”,即遗传信息和表观遗传信息都必须被忠实地复制,这意味着DNA复制机制和表观遗传调节因子之间需要紧密协调。在这篇综述中,我们将重点关注负责哺乳动物DNA甲基化复制和翻译的分子及机制,DNA甲基化是核心表观遗传标记之一。