LTR retrotransposons transcribed in oocytes drive species-specific and heritable changes in DNA methylation

De novo DNA methylation (DNAme) occurs coincident with transcription during mouse oogenesis. As many oocyte transcripts originate in Long Terminal Repeats (LTRs), which are divergent across species, we examined whether polymorphic LTR-initiated transcription units (LITs) shape the oocyte methylome. We identified thousands of syntenic regions in mouse, rat and human, including CpG islands (CGIs), that show divergent DNAme associated with polymorphic LITs. Notably, many CGI promoters methylated exclusively in mouse and/or rat are embedded within rodent-specific LITs, and show persistent maternal methylation in the blastocyst. Polymorphic LITs are also responsible for divergent methylation of CGI promoters in distantly related mouse strains, revealing that LITs also promote intra-species diversification of promoter DNAme. Total RNA-seq in mouse and rat oocytes; H3K36me3 ChIP-seq in mouse oocytes从头DNA甲基化（de novo DNA methylation）发生于小鼠卵子发生过程中，与转录进程同步。由于大量卵子转录本起源于跨物种序列差异较大的长末端重复序列（Long Terminal Repeats, LTRs），本研究探究了多态性长末端重复序列起始转录单元（polymorphic LTR-initiated transcription units, LITs）是否会塑造卵子甲基化组。我们在小鼠、大鼠和人类中鉴定出数千个包含CpG岛（CpG islands, CGIs）的同线区域，这些区域的DNA甲基化差异与多态性LITs相关。值得注意的是，许多仅在小鼠和/或大鼠中发生甲基化的CGI启动子嵌入于啮齿动物特异性LITs内部，并在囊胚中表现出持续的母源甲基化。多态性LITs同样会导致远缘小鼠品系间CGI启动子的甲基化差异，表明LITs可促进启动子DNA甲基化的种内多样化。本数据集包含小鼠与大鼠卵子的总RNA测序（Total RNA-seq）数据，以及小鼠卵子的组蛋白H3赖氨酸36三甲基化（H3K36me3）染色质免疫共沉淀测序（ChIP-seq）数据。