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长链非编码RNA通过调控整体表观遗传修饰和下游基因来影响猪胚胎发育的表观遗传重编程。

LncRNA affects epigenetic reprogramming of porcine embryo development by regulating global epigenetic modification and the downstream gene .

作者信息

Zhang Daoyu, Zhou Yongfeng, Huang Rong, Zhai Yanhui, Wu Di, An Xinglan, Zhang Sheng, Shi Lijing, Li Qi, Kong Xiangjie, Yu Hao, Li Ziyi

机构信息

Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, First Hospital, Jilin University, Changchun, China.

Department of Emergency Medicine, First Hospital, Jilin University, Changchun, China.

出版信息

Front Physiol. 2022 Sep 16;13:971965. doi: 10.3389/fphys.2022.971965. eCollection 2022.

Abstract

The study of preimplantation development is of great significance to reproductive biology and regenerative medicine. With the development of high-throughput deep sequencing technology, it has been found that lncRNAs play a very important role in the regulation of embryonic development. In this study, key lncRNAs that regulate embryonic development were screened by analyzing the expression pattern of lncRNAs in porcine fertilization (IVV) embryos. By knocking down lncRNA expression in fertilization (IVF) embryos, we investigated its function and mechanism of regulating embryonic development. The results showed that the expression pattern of lncRNA was consistent with the time of gene activation. The lncRNAs were highly expressed in the 4-cell to blastocyst stage but barely expressed in the oocytes and 2-cell stage. So we speculated this part of lncRNAs may regulate gene expression. The lncRNA LOC102165808 (named because the gene near this lncRNA is ) was one of them. The knockdown (KD) of inhibited embryonic development, resulting in decreased H3K4me3, H3K4me2, and H3K9me3, and increased DNA methylation. Meanwhile, RNAseq showed was the top decreased gene in KD embryos. There was a severe blastocyst formation defect in KD embryos. Both and could affect and induce more cell apoptosis. In conclusion, the knockdown of inhibits embryonic development by regulating H3K4me3, H3K4me2, DNA methylation, pluripotency gene, and apoptosis, and is one of the downstream genes of in regulating embryonic development.

摘要

植入前发育的研究对生殖生物学和再生医学具有重要意义。随着高通量深度测序技术的发展,人们发现长链非编码RNA(lncRNAs)在胚胎发育调控中发挥着非常重要的作用。在本研究中,通过分析猪体外受精(IVV)胚胎中lncRNAs的表达模式,筛选出调控胚胎发育的关键lncRNAs。通过敲低体外受精(IVF)胚胎中的lncRNA表达,我们研究了其调控胚胎发育的功能和机制。结果表明,lncRNA的表达模式与基因激活时间一致。lncRNAs在4细胞至囊胚阶段高表达,但在卵母细胞和2细胞阶段几乎不表达。因此我们推测这部分lncRNAs可能调控基因表达。lncRNA LOC102165808(因其附近的基因而命名)就是其中之一。敲低该lncRNA会抑制胚胎发育,导致H3K4me3、HIK4me2和H3K9me3减少,DNA甲基化增加。同时,RNA测序显示该lncRNA是敲低胚胎中表达下降最明显的基因。敲低胚胎中存在严重的囊胚形成缺陷。该lncRNA和另一个lncRNA都能影响多能性基因并诱导更多细胞凋亡。总之,敲低该lncRNA通过调控H3K4me3、H3K4me2、DNA甲基化、多能性基因和细胞凋亡来抑制胚胎发育,并且该lncRNA是调控胚胎发育过程中另一lncRNA的下游基因之一。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2432/9523245/38b381918bc8/fphys-13-971965-g001.jpg

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