<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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| Format: | Article |
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MDPI AG
2023-07-01
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| 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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| author | Xiao-Han Li Ming-Hong Sun Wen-Jie Jiang Dongjie Zhou Song-Hee Lee Geun Heo Zhi Chen Xiang-Shun Cui |
| author_facet | Xiao-Han Li Ming-Hong Sun Wen-Jie Jiang Dongjie Zhou Song-Hee Lee Geun Heo Zhi Chen Xiang-Shun Cui |
| author_sort | Xiao-Han Li |
| collection | DOAJ |
| description | 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. |
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| issn | 1661-6596 1422-0067 |
| language | English |
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| spelling | doaj.art-2cb5394e2e724ade9c3663d01fba74e52023-11-18T23:00:40ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-07-0124151212110.3390/ijms241512121<i>ZSCAN4</i> Regulates Zygotic Genome Activation and Telomere Elongation in Porcine Parthenogenetic EmbryosXiao-Han Li0Ming-Hong Sun1Wen-Jie Jiang2Dongjie Zhou3Song-Hee Lee4Geun Heo5Zhi Chen6Xiang-Shun Cui7Department of Animal Science, Chungbuk National University, Cheongju 28644, Republic of KoreaDepartment of Animal Science, Chungbuk National University, Cheongju 28644, Republic of KoreaDepartment of Animal Science, Chungbuk National University, Cheongju 28644, Republic of KoreaDepartment of Animal Science, Chungbuk National University, Cheongju 28644, Republic of KoreaDepartment of Animal Science, Chungbuk National University, Cheongju 28644, Republic of KoreaDepartment of Animal Science, Chungbuk National University, Cheongju 28644, Republic of KoreaCollege of Animal Science and Technology, Yangzhou University, Yangzhou 225009, ChinaDepartment of Animal Science, Chungbuk National University, Cheongju 28644, Republic of KoreaZinc 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.https://www.mdpi.com/1422-0067/24/15/12121<i>ZSCAN4</i><i>DNMT1</i>DNA methylationtelomere lengthZGAporcine embryos |
| spellingShingle | Xiao-Han Li Ming-Hong Sun Wen-Jie Jiang Dongjie Zhou Song-Hee Lee Geun Heo Zhi Chen Xiang-Shun Cui <i>ZSCAN4</i> Regulates Zygotic Genome Activation and Telomere Elongation in Porcine Parthenogenetic Embryos International Journal of Molecular Sciences <i>ZSCAN4</i> <i>DNMT1</i> DNA methylation telomere length ZGA porcine embryos |
| title | <i>ZSCAN4</i> Regulates Zygotic Genome Activation and Telomere Elongation in Porcine Parthenogenetic Embryos |
| title_full | <i>ZSCAN4</i> Regulates Zygotic Genome Activation and Telomere Elongation in Porcine Parthenogenetic Embryos |
| title_fullStr | <i>ZSCAN4</i> Regulates Zygotic Genome Activation and Telomere Elongation in Porcine Parthenogenetic Embryos |
| title_full_unstemmed | <i>ZSCAN4</i> Regulates Zygotic Genome Activation and Telomere Elongation in Porcine Parthenogenetic Embryos |
| title_short | <i>ZSCAN4</i> Regulates Zygotic Genome Activation and Telomere Elongation in Porcine Parthenogenetic Embryos |
| title_sort | i zscan4 i regulates zygotic genome activation and telomere elongation in porcine parthenogenetic embryos |
| topic | <i>ZSCAN4</i> <i>DNMT1</i> DNA methylation telomere length ZGA porcine embryos |
| url | https://www.mdpi.com/1422-0067/24/15/12121 |
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