Szyf Moshe
Department of Pharmacology and Therapeutics, Sackler Program in Epigenetics and Psychobiology, McGill University, Montreal, Que., Canada.
Chem Immunol Allergy. 2012;98:85-99. doi: 10.1159/000336503. Epub 2012 Jun 26.
DNA methylation is an enzymatic modification of the DNA molecule that confers unique differential identities upon similar DNA sequences. DNA methylation plays a critical role in cellular differentiation by conferring cell-type identity upon differentiated tissues in multicellular organisms by an innate developmentally programmed process. Recent data points to the possibility that DNA methylation plays a role in responding to external cues and conferring environment-context identity to DNA. DNA methylation is implicated in the response to early life social environment and might be playing an important role in setting up stable behavioral phenotypes in response to early-life social environment. The critical question is whether these responses are limited to the brain or involve the immune system as well. Addressing this question has important implications on understanding the mechanisms involved in DNA methylation mediated responses to the environment and how they impact the phenotype as well as on the possibility of studying the associations between DNA methylation and behavior and behavioral pathologies in living humans. A model is presented suggesting that DNA methylation acts as a mechanism of genome adaptation to the environment that is genomewide and systemwide. New data suggesting associations between DNA methylation patterns in white blood cells and the social environment will be discussed.
DNA甲基化是DNA分子的一种酶促修饰，它赋予相似的DNA序列独特的差异特征。在多细胞生物中，DNA甲基化通过一个内在的发育编程过程，赋予分化组织细胞类型特征，从而在细胞分化中发挥关键作用。最新数据表明，DNA甲基化可能在响应外部线索以及赋予DNA环境背景特征方面发挥作用。DNA甲基化与早期生活社会环境的反应有关，可能在建立对早期生活社会环境的稳定行为表型方面发挥重要作用。关键问题在于这些反应是否仅限于大脑，还是也涉及免疫系统。解决这个问题对于理解DNA甲基化介导的环境反应机制及其如何影响表型，以及研究DNA甲基化与活体人类行为及行为病理学之间的关联可能性具有重要意义。本文提出了一个模型，表明DNA甲基化作为一种全基因组和全系统的基因组适应环境的机制。将讨论关于白细胞中DNA甲基化模式与社会环境之间关联的新数据。
