Our knowledge of genomic imprinting in primates is lagging behind that of mice largely because of the difficulties of allelic analyses in outbred animals. To understand imprinting dynamics in primates, we profiled transcriptomes, DNA methylomes, and H3K27me3 in uniparental monkey embryos. We further developed single-nucleotide-polymorphism (SNP)-free methods, TARSII and CARSII, to identify germline differentially methylated regions (DMRs) in somatic tissues. Our comprehensive analyses showed that allelic DNA methylation, but not H3K27me3, is a major mark that correlates with paternal-biasedly expressed genes (PEGs) in uniparental monkey embryos. Interestingly, primate germline DMRs are different from PEG-associated DMRs in early embryos and are enriched in placenta. Strikingly, most placenta-specific germline DMRs are lost in placenta of cloned monkeys. Collectively, our study establishes SNP-free germline DMR identification methods, defines developmental imprinting dynamics in primates, and demonstrates imprinting defects in cloned monkey placenta, which provides important clues for improving primate cloning.

我们对灵长类动物基因组印记的了解落后于小鼠，主要是因为远交动物等位基因分析的困难。为了了解灵长类动物的印记动力学，我们分析了单亲猴胚胎中的转录组、DNA 甲基化组和 H3K27me3。我们进一步开发了无单核苷酸多态性 (SNP) 的方法 TARSII 和 CARSII，以识别体细胞组织中的种系差异甲基化区域 (DMR)。我们的综合分析表明，等位基因 DNA 甲基化，而不是 H3K27me3，是与单亲猴胚胎中父本偏向表达基因 (PEG) 相关的主要标志。有趣的是，灵长类生殖系 DMR 与早期胚胎中的 PEG 相关 DMR 不同，并且富含胎盘。引人注目的是，大多数胎盘特异性种系 DMR 在克隆猴的胎盘中丢失。总的来说，我们的研究建立了无 SNP 的生殖系 DMR 鉴定方法，定义了灵长类动物的发育印记动力学，并证明了克隆猴胎盘的印记缺陷，为改进灵长类动物的克隆提供了重要线索。