Transgenerational sperm DMRs escape DNA methylation erasure during embryonic development and epigenetic inheritance.
Transgenerational sperm DMRs escape DNA methylation erasure during embryonic development and epigenetic inheritance.
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DOI：
10.1093/eep/dvad003
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发表时间：
2023
影响因子：
3.8
通讯作者：
中科院分区：
文献类型：
--
作者：
表观遗传信息的种系传递是表观遗传的重要组成部分。以前的研究表明，在桑椹胚中发育干细胞需要消除DNA甲基化。一个例外情况是，印记基因逃脱了DNA甲基化的擦除。跨代差异DNA甲基化区域(DMRS)被推测为印迹样并逃脱了这种消除。目前的研究旨在评估桑椹胚是否能逃脱二氯二苯基三氯乙烷诱导的跨代精子DMR甲基化的消除。观察表明，大多数(98%)跨代精子DMR位点保留了DNA甲基化，而不是被擦除，因此看起来类似于印迹样位点。有趣的是，观察还表明，与精子相比，桑椹胚中大多数低密度CpG基因组位置的DNA甲基化显著增加。这与之前观察到的高密度CpG位点的DNA甲基化擦除形成对比。胚胎发育过程中DNA甲基化的一般擦除似乎适用于高密度DNA甲基化位点(如CpG岛)，但既不适用于跨代DMR甲基化位点，也不适用于构成基因组DNA甲基化位点绝大多数的低密度CpG沙漠。表观遗传学在胚胎发育过程中的作用似乎比DNA甲基化的简单擦除更有活力。
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.
影响因子：
4.4
作者：
Skinner MK;Guerrero-Bosagna C
通讯作者：
Guerrero-Bosagna C