Ben Maamar Millissia, Wang Yue, Nilsson Eric E, Beck Daniel, Yan Wei, Skinner Michael K
Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, WA 99164, USA.
David Geffen School of Medicine at UCLA, The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
Environ Epigenet. 2023 Jun 3;9(1):dvad003. doi: 10.1093/eep/dvad003. eCollection 2023.
Germline transmission of epigenetic information is a critical component of epigenetic inheritance. Previous studies have suggested that an erasure of DNA methylation is required to develop 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 be imprinted-like and escape this erasure. The current study was designed to assess if morula embryos escape the erasure of dichlorodiphenyltrichloroethane-induced transgenerational sperm DMR methylation. Observations demonstrate that the majority (98%) of transgenerational sperm DMR sites retain DNA methylation and are not erased, so appearing similar to imprinted-like sites. Interestingly, observations also demonstrate that the majority of low-density CpG genomic sites had a significant increase in DNA methylation in the morula embryo compared to sperm. This is in contrast to the previously observed DNA methylation erasure of higher-density CpG sites. The general erasure of DNA methylation during embryogenesis appears applicable to high-density DNA methylation sites (e.g. CpG islands) but neither to transgenerational DMR methylation sites nor to low-density CpG deserts, which constitute the vast majority of the genome's DNA methylation sites. The role of epigenetics during embryogenesis appears more dynamic than the simple erasure of DNA methylation.
表观遗传信息的种系传递是表观遗传继承的关键组成部分。先前的研究表明，桑椹胚发育成干细胞需要消除DNA甲基化。一个例外是那些逃避这种DNA甲基化消除的印记基因。跨代差异DNA甲基化区域（DMR）被推测类似印记基因且能逃避这种消除。本研究旨在评估桑椹胚是否能逃避二氯二苯三氯乙烷诱导的跨代精子DMR甲基化的消除。观察结果表明，大多数（98%）跨代精子DMR位点保留了DNA甲基化且未被消除，因此看起来类似于印记样位点。有趣的是，观察结果还表明，与精子相比，桑椹胚中大多数低密度CpG基因组位点的DNA甲基化显著增加。这与之前观察到的高密度CpG位点的DNA甲基化消除情况相反。胚胎发育过程中DNA甲基化的普遍消除似乎适用于高密度DNA甲基化位点（如CpG岛），但不适用于跨代DMR甲基化位点和低密度CpG荒漠，而后者构成了基因组中绝大多数的DNA甲基化位点。胚胎发育过程中表观遗传学的作用似乎比简单的DNA甲基化消除更为动态。
