College of Veterinary Medicine, Northwest A&F University, Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Yangling, Shaanxi, China.
Reproduction. 2019 Jan;157(1):115-126. doi: 10.1530/REP-18-0336.
Endogenous retroviruses (ERVs), which are abundant in mammalian genomes, can modulate the expression of nearby genes, and their expression is dynamic and stage-specific during early embryonic development in mice and humans. However, the functions and mechanisms of ERV elements in regulating embryonic development remain unclear. Here, we utilized several methods to determine the contribution of ERVs to the makeup and regulation of transcripts during embryonic genome activation (EGA). We constructed an ERV library and embryo RNA-seq library (IVF_2c and IVF_8c) of goat to serve as our research basis. The GO and KEGG analysis of nearby ERV genes revealed that some ERV elements may be associated with embryonic development. RNA-seq results were consistent with the features of EGA. To obtain the transcripts derived from the ERV sequences, we blasted the ERV sequences with embryonic transcripts and identified three lncRNAs and one mRNA that were highly expressed in IVF-8c rather than in IVF-2c (q-value <0.05). Then, we validated the expression patterns of nine ERV-related transcripts during early developmental stages and knocked down three high-expression transcripts in EGA. The knockdown of lncRNA TCONS_00460156 or mRNA HSD17B11 significantly decreased the developmental rate of IVF embryos. Our findings suggested that some transcripts from ERVs are essential for the early embryonic development of goat, and analyzing the ERV expression profile during goat EGA may help elucidate the molecular mechanisms of ERV in regulating embryonic development.
内源性逆转录病毒 (ERVs) 在哺乳动物基因组中大量存在,可调节附近基因的表达,其在小鼠和人类早期胚胎发育过程中的表达具有动态性和阶段特异性。然而,ERV 元件在调节胚胎发育中的功能和机制仍不清楚。在这里,我们利用几种方法来确定 ERV 在调控胚胎基因组激活 (EGA) 过程中转录本的组成和调控中的作用。我们构建了一个 ERV 文库和山羊胚胎 RNA-seq 文库 (IVF_2c 和 IVF_8c) 作为我们的研究基础。附近 ERV 基因的 GO 和 KEGG 分析表明,一些 ERV 元件可能与胚胎发育有关。RNA-seq 结果与 EGA 的特征一致。为了获得来自 ERV 序列的转录本,我们将 ERV 序列与胚胎转录本进行比对,鉴定出三个在 IVF-8c 中高度表达而不在 IVF-2c 中表达的 lncRNA 和一个 mRNA (q 值<0.05)。然后,我们在早期发育阶段验证了九个与 ERV 相关的转录本的表达模式,并在 EGA 中敲低了三个高表达的转录本。lncRNA TCONS_00460156 或 mRNA HSD17B11 的敲低显著降低了 IVF 胚胎的发育速度。我们的研究结果表明,一些来自 ERV 的转录本对于山羊的早期胚胎发育是必不可少的,分析山羊 EGA 期间 ERV 的表达谱可能有助于阐明 ERV 调节胚胎发育的分子机制。