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ELF4对猪早期胚胎发育过程中的合子基因激活和表观遗传重编程至关重要。

ELF4 is critical to zygotic gene activation and epigenetic reprogramming during early embryonic development in pigs.

作者信息

Shi Lijing, Zhai Yanhui, Zhao Yuanshen, Kong Xiangjie, Zhang Daoyu, 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.

College of Animal Science, Jilin University, Changchun, China.

出版信息

Front Vet Sci. 2022 Jul 19;9:954601. doi: 10.3389/fvets.2022.954601. eCollection 2022.

Abstract

Zygotic gene activation (ZGA) and epigenetic reprogramming are critical in early embryonic development in mammals, and transcription factors are involved in regulating these events. However, the effects of ELF4 on porcine embryonic development remain unclear. In this study, the expression of ELF4 was detected in early porcine embryos and different tissues. By knocking down ELF4, the changes of H3K9me3 modification, DNA methylation and ZGA-related genes were analyzed. Our results showed that was expressed at all stages of early porcine embryos fertilized (IVF), with the highest expression level at the 8-cell stage. The embryonic developmental competency and blastocyst quality decreased after ELF4 knockdown (20.70% control vs. 17.49% si-scramble vs. 2.40% si-; < 0.001). Knockdown of ELF4 induced DNA damage at the 4-cell stage. Interfering with ELF4 resulted in abnormal increases in H3K9me3 and DNA methylation levels at the 4-cell stage and inhibited the expression of genes related to ZGA. These results suggest that ELF4 affects ZGA and embryonic development competency in porcine embryos by maintaining genome integrity and regulating dynamic changes of H3K9me3 and DNA methylation, and correctly activating ZGA-related genes to promote epigenetic reprogramming. These results provide a theoretical basis for further studies on the regulatory mechanisms of ELF4 in porcine embryos.

摘要

合子基因激活(ZGA)和表观遗传重编程在哺乳动物早期胚胎发育中至关重要,转录因子参与调控这些过程。然而,ELF4对猪胚胎发育的影响仍不清楚。在本研究中,检测了ELF4在猪早期胚胎和不同组织中的表达。通过敲低ELF4,分析了H3K9me3修饰、DNA甲基化和ZGA相关基因的变化。我们的结果表明,ELF4在体外受精(IVF)的猪早期胚胎的各个阶段均有表达,在8细胞阶段表达水平最高。敲低ELF4后,胚胎发育能力和囊胚质量下降(对照组为20.70%,干扰对照组为17.49%,干扰ELF4组为2.40%;P<0.001)。敲低ELF4在4细胞阶段诱导DNA损伤。干扰ELF4导致4细胞阶段H3K9me3和DNA甲基化水平异常升高,并抑制了ZGA相关基因的表达。这些结果表明,ELF4通过维持基因组完整性以及调控H3K9me3和DNA甲基化的动态变化,并正确激活ZGA相关基因以促进表观遗传重编程,从而影响猪胚胎中的ZGA和胚胎发育能力。这些结果为进一步研究ELF4在猪胚胎中的调控机制提供了理论依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77fe/9343831/996785a60713/fvets-09-954601-g0001.jpg

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