Parental DNA methylation and histone modifications undergo distinct global reprogramming in mammalian pre-implantation embryos, but the landscape of epigenetic crosstalk and its effects on embryogenesis are largely unknown. Here we comprehensively analyse the association between DNA methylation and H3K9me3 reprogramming in mouse pre-implantation embryos and reveal that CpG-rich genomic loci with high H3K9me3 signal and DNA methylation level (CHM) are hotspots of DNA methylation maintenance during pre-implantation embryogenesis. We further profile the allele-specific epigenetic map with unprecedented resolution in gynogenetic and androgenetic embryos, respectively, and identify 1,279 allele-specific CHMs, including 19 known imprinting control regions (ICRs). Our study suggests that 22 ICR-like regions (ICRLRs) may regulate allele-specific transcription similarly to known ICRs, and five of them are confirmed to be important for mouse embryo development. Taken together, our study reveals the widespread existence of allele-specific CHMs and largely extends the scope of allele-specific regulation in mammalian pre-implantation embryos.

亲本 DNA 甲基化和组蛋白修饰在哺乳动物植入前胚胎中经历了明显的全局重编程，但表观遗传串扰及其对胚胎发生的影响在很大程度上是未知的。在这里，我们全面分析了小鼠植入前胚胎中 DNA 甲基化与 H3K9me3 重编程之间的关联，并揭示具有高 H3K9me3 信号和 DNA 甲基化水平 (CHM) 的富含 CpG 的基因组位点是植入前胚胎发生过程中 DNA 甲基化维持的热点。我们进一步分析了等位基因特异性表观遗传图谱，分别以前所未有的分辨率在雌性发育和雄性发育胚胎中，并确定了 1,279 个等位基因特异性 CHM，包括 19 个已知的印记控制区 (ICR)。我们的研究表明，22 个 ICR 样区域 (ICRLRs) 可能与已知的 ICRs 类似地调节等位基因特异性转录，其中五个被证实对小鼠胚胎发育很重要。总之，我们的研究揭示了等位基因特异性 CHM 的广泛存在，并在很大程度上扩展了哺乳动物植入前胚胎中等位基因特异性调控的范围。