Kubota Takeo
Department of Epigenetic Medicine, Faculty of Medicine, University of Yamanashi, Yamanashi, 409-3898, Japan.
Environ Epigenet. 2016 Aug 8;2(3):dvw017. doi: 10.1093/eep/dvw017. eCollection 2016 Aug.
Epigenetics is a gene regulation mechanism that does not depend on genomic DNA sequences but depends on chemical modification of genomic DNA and histone proteins around which DNA is wrapped. The failure of epigenetic mechanisms is known to cause various congenital disorders. It is also known that the failures of epigenetic mechanisms causes various acquired disorders since epigenetic modifications of the genome (i.e., "epigenome") are more vulnerable to environmental stress, such as malnutrition, environmental chemicals, and mental stress, than the "genome," especially during the early period of life. However, the epigenome has a reversible property since it is based on removable residues on genomic DNA. Thus, environmentally induced epigenomic alterations can be potentially restored. In fact, some medicines, especially for psychiatric diseases, are known to restore an altered epigenome, resulting in the correction of gene expression. Several lines of evidence suggest that environmentally induced epigenomic alterations are not erased completely during gametogenesis, but are transmitted to subsequent generations with disease phenotypes. In accordance with these understandings, I would like to propose the development of epigenomic-based preemptive medicine that consists of the early detection of the developmental origins of diseases using epigenomic signatures and the early intervention that take advantages of the use of epigenomic reversibility.
表观遗传学是一种基因调控机制，它不依赖于基因组DNA序列，而是依赖于基因组DNA以及包裹DNA的组蛋白的化学修饰。已知表观遗传机制的失效会导致各种先天性疾病。还已知表观遗传机制的失效会导致各种后天性疾病，因为基因组（即“表观基因组”）的表观遗传修饰比“基因组”更容易受到环境压力的影响，如营养不良、环境化学物质和精神压力，尤其是在生命早期。然而，表观基因组具有可逆性，因为它基于基因组DNA上可去除的残基。因此，环境诱导的表观基因组改变有可能被恢复。事实上，一些药物，尤其是治疗精神疾病的药物，已知可以恢复改变的表观基因组，从而纠正基因表达。有几条证据表明，环境诱导的表观基因组改变在配子发生过程中不会完全消除，而是会与疾病表型一起传递给后代。基于这些认识，我提议开发基于表观基因组的预防医学，它包括利用表观基因组特征早期检测疾病的发育起源以及利用表观基因组可逆性进行早期干预。
