表观遗传信息的跨代传递

How can epigenetic information be inherited to the next generation?

表观遗传是不依赖于DNA序列改变的染色质变化所引起的遗传现象.表观遗传学作为调控环境诱导的表型的机器,通过调控基因在时间和空间的特异性表达,将个体获得的性状传递给子代.表观遗传信息跨代传递的证据逐年涌现,亲代饮食、生活经历以及生活习惯等可影响子代的代谢以及对应激的响应,而表观遗传信息主要由DNA甲基化、小RNA、组蛋白修饰、染色体的状态、转录因子的丰度以及阮病毒等6种载体传递.本文重点探讨了DNA甲基化和小RNA介导的表观遗传信息跨代传递,包括印记基因和非印记基因的DNA甲基化改变以及精子中mi RNA和t RNA片段介导的后代性状改变.鉴于外界环境的复杂性和不可控性以及表观遗传修饰的可塑性,表观遗传信息跨代传递的研究也面临诸多挑战,但新的方法和测序技术为揭示表观遗传信息的跨代传递的分子机制提供了新的机遇.基于表观遗传信息的跨代传递,我们应重新认识体外受精、基于遗传学的药物设计等社会问题对后代潜在的影响,为预防相关疾病及政策制定提供新的视角.

Epigenetics refers to the study of stably heritable phenotype resulting from changes in chromatin without alterations in the DNA sequence. Epigenetics regulates specific gene expression in a spatial-temporal manner, and is able to transmit the acquired trait to the next generation. Epigenetics mainly consists of DNA methylation, histone modification and non-coding RNAs, though yet only the former 2 proved to be reversible and all hereditable, implying that epigenetics functions as an adaptive approach to sensing environmental factors. Evidences of transgenerational epigenetic inheritance, in which the effects that parental diet, life experience and habits have on the progeny＇s metabolism and their responses to stress have been highly emphasized and extensively studied, have been emerging annually. Epigenetic information is mainly transmitted through 6 carriers, i.e. DNA methylation, small RNAs, histone modifications, chromatin remodelling, transcription factor abundance and prions. Here, we primarily focus on the transgenerational epigenetic inheritance mediated by DNA methylation and small RNAs, discussion on which is divided into two sections： （1） DNA-methylation-mediated transgenerational epigenetic inheritance. Both DNA methylation alteration of imprinted genes （such as IGF2） and non-imprinted genes could modulate their expression, further transforming the phenotype. （2） ncRNAs-mediated transgenerational epigenetic inheritance. It＇s transparent that mammalian sperm contains various ncRNAs, including rRNAs, piRNAs, miRNAs, tRNAs and their fragments. Here, the latter 3 have been confirmed to be involved in transmission of epigenetic information generally triggered by environmental factors. It＇s highlighted here that DNA methylation and ncRNAs are capable of coordinating each other to collectively contribute to the transgenerational epigenetic inheritance. Owing to the complexity of the environment and dynamic plasticity of epigenetic modifications, studies on transgenerational epigenetic inheritance face many barriers. Firstly, a substantial amount of results are achieved by epidemiological analysis, the raw data of which could date back to few decades ago. The canonical cases are the 1944-1945 Dutch Hunger Winter and Chinese Famine of 1959-1961. It severely weakens their reliability. Secondly, even a single environmental factor is powerful enough to generate diverse epigenetic alternations in downstream genes. When multiple factors involved in a single study are taken into consideration, it becomes extremely difficult to distinguish the pivotal factors and genes in the regulatory network. Despite what appears to be a grim situation at hand, the advent of novel methods and technologies continues to shed light on the molecular mechanism of epigenetic inheritance. Lastly, it is essential to concurrently rethink and reevaluate the potential impacts of certain social issues linked to epigenetics, such as in vitro fertilization, genetics-based drug design. Understanding these impacts will offer a new angle to be considered in the policy making of related disease prevention.