Ficz Gabriella
Centre for Haemato-Oncology, Barts Cancer Institute, London EC1M 6BQ, UK
J Exp Biol. 2015 Jan 1;218(Pt 1):14-20. doi: 10.1242/jeb.107961.
From a fertilised egg to a mature organism, cells divide and accumulate epigenetic information, which is faithfully passed on to daughter cells. DNA methylation consolidates the memory of the developmental history and, albeit very stable, it is not immutable and DNA methylation patterns can be deconstructed – a process that is essential to regain totipotency. Research into DNA methylation erasure gained momentum a few years ago with the discovery of 5-hydroxymethylcytosine, an oxidation product of 5-methylcytosine. The role of this new epigenetic modification in DNA demethylation and other potential epigenetic roles are discussed here. But what are the mechanisms that regulate deposition of epigenetic modifications? Until recently, limited direct evidence indicated that signalling molecules are able to modulate the function of epigenetic modifiers, which shape the epigenome in the nucleus of the cell. New reports in embryonic stem cell model systems disclosed a tight relationship between major signalling pathways and the DNA methylation machinery, which opens up exciting avenues in the relationship between external signals and epigenetic memory. Here, I discuss mechanisms and concepts in DNA methylation patterning, the implications in normal development and disease, and future directions.
从受精卵发育成成熟生物体的过程中，细胞不断分裂并积累表观遗传信息，这些信息会如实地传递给子细胞。DNA甲基化巩固了发育历史的记忆，尽管它非常稳定，但并非一成不变，DNA甲基化模式可以被解构——这是恢复全能性所必需的过程。几年前，随着5-羟甲基胞嘧啶（5-甲基胞嘧啶的氧化产物）的发现，对DNA甲基化消除的研究开始兴起。本文将讨论这种新的表观遗传修饰在DNA去甲基化中的作用以及其他潜在的表观遗传作用。但是，调控表观遗传修饰沉积的机制是什么呢？直到最近，有限的直接证据表明信号分子能够调节表观遗传修饰因子的功能，这些修饰因子塑造了细胞核中的表观基因组。胚胎干细胞模型系统中的新报告揭示了主要信号通路与DNA甲基化机制之间的紧密关系，这为外部信号与表观遗传记忆之间的关系开辟了令人兴奋的研究途径。在此，我将讨论DNA甲基化模式形成的机制和概念、其在正常发育和疾病中的意义以及未来的研究方向。
