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.

中文翻译：

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精子 ncRNA 指导的 DNA 甲基化和 DNA 甲基化指导的组蛋白保留在表观遗传跨代遗传中的整合

环境诱导的表观遗传病理学和表型变异的跨代遗传已在从植物到人类的所有生物体中得到证实。这种非遗传形式的遗传是通过精子和/或卵子的表观遗传改变介导到后代的。尽管差异 DNA 甲基化区域 (DMR)、非编码 RNA (ncRNA) 和差异组蛋白保留 (DHR) 的联合调控已被证明存在，但这些不同表观遗传过程的整合仍有待阐明。当前的研究旨在检查不同表观遗传过程的整合。采用 F0 代妊娠雌性短暂暴露于农业杀菌剂乙烯菌核利或杀虫剂 DDT（二氯二苯基三氯乙烷）的大鼠模型，用于从成年雄性中获取后续 F1 代后代、F2 代孙代和 F3 代大代的精子。 -孙子。F1 代精子 ncRNA 与 F1、F2 和 F3 代 DMR 有大量重叠，表明 RNA 指导的 DNA 甲基化具有潜在作用。DMR 与 DHR 也有显着重叠，表明潜在的 DNA 甲基化指导的组蛋白保留。此外，F1代精子中诱导的DMRs的高比例在后续世代中得以维持。许多 DMR、ncRNA 和 DHR 共定位于相同的染色体定位区域。观察结果表明，DMR、ncRNA 和 DHR 的整合部分涉及表观遗传跨代遗传中 RNA 指导的 DNA 甲基化和 DNA 甲基化指导的组蛋白保留。