Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, WA, 99164-4236, USA.
Epigenetics Chromatin. 2021 Jan 12;14(1):6. doi: 10.1186/s13072-020-00378-0.
Environmentally induced epigenetic transgenerational inheritance of pathology and phenotypic variation has been demonstrated in all organisms investigated from plants to humans. This non-genetic form of inheritance is mediated through epigenetic alterations in the sperm and/or egg to subsequent generations. Although the combined regulation of differential DNA methylated regions (DMR), non-coding RNA (ncRNA), and differential histone retention (DHR) have been shown to occur, the integration of these different epigenetic processes remains to be elucidated. The current study was designed to examine the integration of the different epigenetic processes.
A rat model of transiently exposed F0 generation gestating females to the agricultural fungicide vinclozolin or pesticide DDT (dichloro-diphenyl-trichloroethane) was used to acquire the sperm from adult males in the subsequent F1 generation offspring, F2 generation grand offspring, and F3 generation great-grand offspring. The F1 generation sperm ncRNA had substantial overlap with the F1, F2 and F3 generation DMRs, suggesting a potential role for RNA-directed DNA methylation. The DMRs also had significant overlap with the DHRs, suggesting potential DNA methylation-directed histone retention. In addition, a high percentage of DMRs induced in the F1 generation sperm were maintained in subsequent generations.
Many of the DMRs, ncRNA, and DHRs were colocalized to the same chromosomal location regions. Observations suggest an integration of DMRs, ncRNA, and DHRs in part involve RNA-directed DNA methylation and DNA methylation-directed histone retention in epigenetic transgenerational inheritance.
从植物到人等所有被研究的生物都证明了环境诱导的病理学和表型变异的跨代表观遗传遗传。这种非遗传形式的遗传是通过精子和/或卵子中的表观遗传改变传递给后代的。尽管已经表明差异 DNA 甲基化区域（DMR）、非编码 RNA（ncRNA）和差异组蛋白保留（DHR）的联合调控会发生，但这些不同的表观遗传过程的整合仍有待阐明。本研究旨在研究不同表观遗传过程的整合。
使用暴露于农业杀真菌剂戊唑醇或农药滴滴涕（二氯二苯三氯乙烷）的 F0 代妊娠雌性的大鼠模型，从随后的 F1 代后代、F2 代孙代和 F3 代曾孙代雄性成年雄性中获取精子。F1 代精子中的 ncRNA 与 F1、F2 和 F3 代 DMR 有很大的重叠，这表明 RNA 指导的 DNA 甲基化可能发挥作用。DMR 也与 DHR 有显著重叠，这表明潜在的 DNA 甲基化指导组蛋白保留。此外，F1 代精子中诱导的 DMR 有很大一部分在随后的世代中得到维持。
许多 DMR、ncRNA 和 DHR 都被定位到相同的染色体位置区域。观察结果表明，DMR、ncRNA 和 DHR 的整合部分涉及 RNA 指导的 DNA 甲基化和 DNA 甲基化指导的组蛋白保留，这在跨代表观遗传遗传中发挥作用。
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