<i>ZSCAN4</i> Regulates Zygotic Genome Activation and Telomere Elongation in Porcine Parthenogenetic Embryos

Zinc finger and SCAN domain-containing 4 (<i>ZSCAN4</i>), a DNA-binding protein, maintains telomere length and plays a key role in critical aspects of mouse embryonic stem cells, including maintaining genomic stability and defying cellular senescence. However, the effect of <i>ZSCA...

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Bibliographic Details
Main Authors: Xiao-Han Li, Ming-Hong Sun, Wen-Jie Jiang, Dongjie Zhou, Song-Hee Lee, Geun Heo, Zhi Chen, Xiang-Shun Cui
Format: Article
Language:English
Published: MDPI AG 2023-07-01
Series:International Journal of Molecular Sciences
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Online Access:https://www.mdpi.com/1422-0067/24/15/12121
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Summary:Zinc finger and SCAN domain-containing 4 (<i>ZSCAN4</i>), a DNA-binding protein, maintains telomere length and plays a key role in critical aspects of mouse embryonic stem cells, including maintaining genomic stability and defying cellular senescence. However, the effect of <i>ZSCAN4</i> in porcine parthenogenetic embryos remains unclear. To investigate the function of <i>ZSCAN4</i> and the underlying mechanism in porcine embryo development, <i>ZSCAN4</i> was knocked down via dsRNA injection in the one-cell stage. <i>ZSCAN4</i> was highly expressed in the four- and five- to eight-cell stages in porcine embryos. The percentage of four-cell stage embryos, five- to eight-cell stage embryos, and blastocysts was lower in the <i>ZSCAN4</i> knockdown group than in the control group. Notably, depletion of <i>ZSCAN4</i> induced the protein expression of <i>DNMT1</i> and 5-Methylcytosine (5mC, a methylated form of the DNA base cytosine) in the four-cell stage. The H3K27ac level and ZGA genes expression decreased following <i>ZSCAN4</i> knockdown. Furthermore, <i>ZSCAN4</i> knockdown led to DNA damage and shortened telomere compared with the control. Additionally, <i>DNMT1</i>-dsRNA was injected to reduce DNA hypermethylation in <i>ZSCAN4</i> knockdown embryos. <i>DNMT1</i> knockdown rescued telomere shortening and developmental defects caused by <i>ZSCAN4</i> knockdown. In conclusion, <i>ZSCAN4</i> is involved in the regulation of transcriptional activity and is essential for maintaining telomere length by regulating <i>DNMT1</i> expression in porcine ZGA.
ISSN:1661-6596
1422-0067