Transgenerational Sperm DMRs and Low CpG Density Sites Escape Methylation Erasure in Embryonic Epigenetic Inheritance

Previous studies have suggested an erasure of DNA methylation is required to develop the stem cells in the morula embryo. An exception involves imprinted genes that escape this DNA methylation erasure. Transgenerational differential DNA methylation regions (DMRs) have been speculated to also escape this erasure. The current study was designed to assess if morula embryos escape erasure of DDT (dichloro-diphenyl-trichloroethane)-induced transgenerational sperm DMRs. Observations demonstrate that the transgenerational sperm DMR sites are not erased, so are imprinted-like DMR sites. Interestingly, we also found that the majority of low-density CpG genomic sites had a significant increase in DNA methylation in the morula embryo compared to sperm. The general erasure of DNA methylation during embryogenesis appears applicable for high-density CpG islands, but not low-density CpG deserts.既往研究表明，DNA甲基化（DNA methylation）的消除过程是桑椹胚（morula embryo）发育为干细胞所必需的环节。但存在一类例外：印记基因（imprinted genes）可逃脱该DNA甲基化消除过程。有研究推测，跨代表观遗传差异DNA甲基化区域（Transgenerational differential DNA methylation regions, DMRs）同样可逃脱该消除过程。本研究旨在评估桑椹胚是否可逃脱滴滴涕（DDT，dichloro-diphenyl-trichloroethane）诱导的跨代表观遗传精子差异DNA甲基化区域的消除。观测结果显示，跨代表观遗传精子差异DNA甲基化位点并未被消除，类印记基因差异DNA甲基化位点亦是如此。值得注意的是，本研究还发现，相较于精子细胞，桑椹胚中多数低密度CpG基因组位点的DNA甲基化水平显著升高。胚胎发生过程中DNA甲基化的普遍消除现象，似乎仅适用于高密度CpG岛（CpG islands），而非低密度CpG荒漠（CpG deserts）。