Jeltsch Albert, Broche Julian, Bashtrykov Pavel
Institute of Biochemistry and Technical Biochemistry, Department of Biochemistry, University of Stuttgart, 70569 Stuttgart, Germany.
Genes (Basel). 2018 Nov 21;9(11):566. doi: 10.3390/genes9110566.
DNA methylation is an essential part of the epigenome chromatin modification network, which also comprises several covalent histone protein post-translational modifications. All these modifications are highly interconnected, because the writers and erasers of one mark, DNA methyltransferases (DNMTs) and ten eleven translocation enzymes (TETs) in the case of DNA methylation, are directly or indirectly targeted and regulated by other marks. Here, we have collected information about the genomic distribution and variability of DNA methylation in human and mouse DNA in different genomic elements. After summarizing the impact of DNA methylation on genome evolution including CpG depletion, we describe the connection of DNA methylation with several important histone post-translational modifications, including methylation of H3K4, H3K9, H3K27, and H3K36, but also with nucleosome remodeling. Moreover, we present the mechanistic features of mammalian DNA methyltransferases and their associated factors that mediate the crosstalk between DNA methylation and chromatin modifications. Finally, we describe recent advances regarding the methylation of non-CpG sites, methylation of adenine residues in human cells and methylation of mitochondrial DNA. At several places, we highlight controversial findings or open questions demanding future experimental work.
DNA甲基化是表观基因组染色质修饰网络的重要组成部分，该网络还包括几种组蛋白共价翻译后修饰。所有这些修饰都高度相互关联，因为一种标记（在DNA甲基化中为DNA甲基转移酶（DNMT）和十 - 十一易位酶（TET））的写入和擦除酶直接或间接受其他标记的靶向和调控。在这里，我们收集了关于人类和小鼠DNA中不同基因组元件的DNA甲基化的基因组分布和变异性的信息。在总结DNA甲基化对基因组进化的影响（包括CpG缺失）之后，我们描述了DNA甲基化与几种重要的组蛋白翻译后修饰（包括H3K4、H3K9、H3K27和H3K36的甲基化）的联系，还描述了与核小体重塑的联系。此外，我们介绍了哺乳动物DNA甲基转移酶及其相关因子的机制特征，这些因子介导了DNA甲基化与染色质修饰之间的串扰。最后，我们描述了关于非CpG位点甲基化、人类细胞中腺嘌呤残基甲基化和线粒体DNA甲基化的最新进展。在几个地方，我们突出了有争议的发现或需要未来实验工作的开放性问题。
