Department of Diabetes Complications and Metabolism, Arthur Riggs Diabetes and Metabolism Research Institute, City of Hope, Duarte, CA 91010, USA.
Biomolecules. 2023 Nov 22;13(12):1684. doi: 10.3390/biom13121684.
During gestation, maternal (F0), embryonic (F1), and migrating primordial germ cell (F2) genomes can be simultaneously exposed to environmental influences. Accumulating evidence suggests that operating epi- or above the genetic DNA sequence, covalent DNA methylation (DNAme) can be recorded onto DNA in response to environmental insults, some sites which escape normal germline erasure. These appear to intrinsically regulate future disease propensity, even transgenerationally. Thus, an organism's genome can undergo epigenetic adjustment based on environmental influences experienced by prior generations. During the earliest stages of mammalian development, the three-dimensional presentation of the genome is dramatically changed, and DNAme is removed genome wide. Why, then, do some pathological DNAme patterns appear to be heritable? Are these correctable? In the following sections, I review concepts of transgenerational epigenetics and recent work towards programming transgenerational DNAme. A framework for editing heritable DNAme and challenges are discussed, and ethics in human research is introduced.
在妊娠期间，母体（F0）、胚胎（F1）和迁移的原始生殖细胞（F2）基因组可以同时受到环境影响。越来越多的证据表明，在遗传 DNA 序列上或之上起作用的共价 DNA 甲基化（DNAme）可以在环境损伤时记录在 DNA 上，一些位点逃脱了正常的种系消除。这些似乎内在地调节未来的疾病易感性，甚至跨代。因此，一个生物体的基因组可以根据前几代经历的环境影响进行表观遗传调整。在哺乳动物发育的最早阶段，基因组的三维呈现发生了巨大变化，整个基因组的 DNAme 被去除。那么，为什么一些病理性的 DNAme 模式似乎是可遗传的呢？这些可以纠正吗？在下面的部分中，我将回顾跨代表观遗传学的概念和最近在编程跨代 DNAme 方面的工作。讨论了编辑可遗传 DNAme 的框架和挑战，并介绍了人类研究中的伦理问题。
