Department of Pharmacology and Therapeutics, McGill University, 3655 Sir William Osler Promenade, Montreal, Quebec H3G 1Y6, Canada.
J Genet Genomics. 2013 Jul 20;40(7):331-8. doi: 10.1016/j.jgg.2013.06.004. Epub 2013 Jun 25.
The impact of early physical and social environments on life-long phenotypes is well known. Moreover, we have documented evidence for gene-environment interactions where identical gene variants are associated with different phenotypes that are dependent on early life adversity. What are the mechanisms that embed these early life experiences in the genome? DNA methylation is an enzymatically-catalyzed modification of DNA that serves as a mechanism by which similar sequences acquire cell type identity during cellular differentiation and embryogenesis in the same individual. The hypothesis that will be discussed here proposes that the same mechanism confers environmental-exposure specific identity upon DNA providing a mechanism for embedding environmental experiences in the genome, thus affecting long-term phenotypes. Particularly important is the environment early in life including both the prenatal and postnatal social environments.
早期的生理和社会环境对终身表型的影响是众所周知的。此外,我们已经记录了基因-环境相互作用的证据,相同的基因变异与不同的表型有关,而这些表型取决于早期生活逆境。那么,是什么机制将这些早期的生活经历嵌入基因组中的呢?DNA 甲基化是一种酶促催化的 DNA 修饰,它是一种机制,通过这种机制,在同一个体的细胞分化和胚胎发生过程中,相似的序列获得细胞类型的身份。这里将要讨论的假设提出,相同的机制赋予 DNA 特定的环境暴露身份,从而为将环境经验嵌入基因组提供了一种机制,从而影响长期表型。特别重要的是生命早期的环境,包括产前和产后的社会环境。