Department of Molecular Biology, Lewis Thomas Lab 320, Princeton University, Princeton, NJ 08544, USA.
J Epidemiol Community Health. 2012 Jan;66(1):8-13. doi: 10.1136/jech.2010.130690. Epub 2011 Nov 1.
It is becoming increasingly apparent that genetic factors are inadequate to fully explain many processes that shape development and disease. For example, monozygotic twin pairs, despite sharing identical DNA sequences, are often discordant for many traits and diseases, indicating that the same genotype can give rise to distinct phenotypes. This points towards the involvement of additional factors that cannot be explained solely by the sequence of the genome. Epigenetic modifications, defined as heritable changes that do not alter the nucleotide sequence, emerge as key factors that regulate chromatin structure and gene expression and, together with genetic factors, provide the mechanistic basis to understand the biological effects of various classes of environmental exposures. Epigenetic mechanisms explain the ability of certain chemical compounds to initiate biological perturbations that can lead to malignancy, despite being weak mutagens or lacking mutagenic activity altogether-a view that challenges old beliefs and opens new avenues in public health. The field of epigenetics also explains the causal link between certain infectious diseases and cancer, a relationship that was first observed over a century ago and was initially discounted, then fell into oblivion and more recently re-emerged as an important concept in biology. A key feature that distinguishes epigenetic modifications from genetic changes is their reversible nature. This provides exciting prophylactic and therapeutic perspectives, some of which already materialised with the approval of the first drugs that modulate the epigenetic machinery, reinforcing the idea that our genes are not our destiny.
越来越明显的是,遗传因素不足以完全解释许多塑造发育和疾病的过程。例如,尽管同卵双胞胎共享相同的 DNA 序列,但在许多特征和疾病上往往存在差异,这表明相同的基因型可能产生不同的表型。这表明存在其他不能仅通过基因组序列来解释的因素。表观遗传修饰被定义为可遗传的、不改变核苷酸序列的变化,它是调节染色质结构和基因表达的关键因素,与遗传因素一起为理解各种环境暴露的生物学效应提供了机制基础。表观遗传机制解释了某些化学化合物能够引发生物学扰动的能力,这些扰动可能导致恶性肿瘤,尽管它们是弱诱变剂或完全缺乏诱变活性——这种观点挑战了旧观念,并为公共卫生开辟了新途径。表观遗传学领域还解释了某些传染病和癌症之间的因果关系,这种关系早在一个多世纪前就被首次观察到,并最初被否定,然后被遗忘,最近又重新成为生物学中的一个重要概念。表观遗传修饰与遗传变化的一个关键区别特征是其可逆性。这为预防性和治疗性观点提供了令人兴奋的前景,其中一些已经随着第一批调节表观遗传机制的药物的批准而实现,这进一步证实了我们的基因不是我们命运的观点。