DNA methylation and DNA methyltransferases.
DNA methylation and DNA methyltransferases.
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DOI：
10.1186/s13072-017-0130-8
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发表时间：
2017
影响因子：
3.9
通讯作者：
Bestor TH
中科院分区：
文献类型：
--
作者：
Edwards JR;Yarychkivska O;Boulard M;Bestor TH
关于基因组甲基化模式的形式、功能和调节的流行观点起源于过去许多年，当时哺乳动物基因组的结构还只是模糊的认识，当时编码蛋白质的哺乳动物基因的数量被认为至少是实际数量的五倍，当人们不知道只有10%的基因组处于选择压力下，可能具有生物学功能时。我们使用基因组生物学和全基因组甲基化分析的最新发现，重新评估基因组甲基化模式的形状和它们在配子发生和早期发育过程中所经历的变化的性质。我们观察到，在早期发育过程中甲基化状态发生深刻变化的序列主要是没有调节功能的序列。我们还讨论了最近的研究结果，开始解释显着的保真度的甲基化维持。而不是在哺乳动物中的DNA甲基化的一般概述（这一直是许多评论的主题），我们提出了一个新的分析甲基化的CpG二核苷酸的分布在多个序列区室，构成哺乳动物基因组，我们提供了一个更新的解释发生在生殖细胞和早期胚胎中的甲基化模式的变化的性质。我们讨论的线索，可能指定特定序列的去甲基化或从头甲基化在发展过程中，我们总结了最近的发现机制，保持哺乳动物基因组中的甲基化模式。我们还描述了几种人类疾病，每一种都非常不同，是由DNA甲基转移酶基因突变引起的。
The prevailing views as to the form, function, and regulation of genomic methylation patterns have their origin many years in the past, at a time when the structure of the mammalian genome was only dimly perceived, when the number of protein-encoding mammalian genes was believed to be at least five times greater than the actual number, and when it was not understood that only ~10% of the genome is under selective pressure and likely to have biological function. We use more recent findings from genome biology and whole-genome methylation profiling to provide a reappraisal of the shape of genomic methylation patterns and the nature of the changes that they undergo during gametogenesis and early development. We observe that the sequences that undergo deep changes in methylation status during early development are largely sequences without regulatory function. We also discuss recent findings that begin to explain the remarkable fidelity of maintenance methylation. Rather than a general overview of DNA methylation in mammals (which has been the subject of many reviews), we present a new analysis of the distribution of methylated CpG dinucleotides across the multiple sequence compartments that make up the mammalian genome, and we offer an updated interpretation of the nature of the changes in methylation patterns that occur in germ cells and early embryos. We discuss the cues that might designate specific sequences for demethylation or de novo methylation during development, and we summarize recent findings on mechanisms that maintain methylation patterns in mammalian genomes. We also describe the several human disorders, each very different from the other, that are caused by mutations in DNA methyltransferase genes.