Research Papers:

Dnmt1s in donor cells is a barrier to SCNT-mediated DNA methylation reprogramming in pigs

Xuexiong Song, Zhonghua Liu, Hongbin He, Jianyu Wang, Huatao Li, Jingyu Li, Fangzheng Li, Zhongling Jiang and Yanjun Huan _

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Oncotarget. 2017; 8:34980-34991. https://doi.org/10.18632/oncotarget.16507

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Xuexiong Song1,*, Zhonghua Liu2,*, Hongbin He3,*, Jianyu Wang4, Huatao Li1, Jingyu Li2, Fangzheng Li1, Zhongling Jiang1 and Yanjun Huan1

1College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, Shandong Province, China

2College of Life Science, Northeast Agricultural University, Harbin, Heilongjiang Province, China

3College of Life Science, Shandong Normal University, Jinan, Shandong Province, China

4Institute of Life Science, Chongqing Medical University, Chongqing, China

*These authors have contributed equally to this work

Correspondence to:

Yanjun Huan, email: huanyanjun1982@163.com

Keywords: Dnmt1s, DNA methylation reprogramming, somatic cell nuclear transfer, embryo, pig

Received: December 23, 2016    Accepted: March 09, 2017    Published: March 23, 2017


Low development of somatic cell nuclear transfer embryos could be due to the incomplete DNA methylation reprogramming, and Dnmt1s existing in donor cells may be one cause of this disrupted DNA methylation reprogramming. However, the reprogramming pattern of Dnmt1s and its effect on DNA methylation reprogramming in cloned embryos remain poorly understood. Here, we displayed that along with the significantly higher Dnmt1 expression at the zygotic gene activation stage of cloned embryos, genomic methylation level was markedly upregulated, and the arrested rate was significantly higher compared with their in vitro fertilization counterparts. Then, we demonstrated that Dnmt1s, not Dnmt1o, methylation and expression levels in cloned embryos were significantly higher from the 1-cell to 4-cell stage but markedly lower at the blastocyst stage. When Dnmt1s in donor cells was appropriately removed, more cloned embryos passed through the zygotic gene activation stage and the blastocyst rate significantly increased. Furthermore, Dnmt1s knockdown significantly improved itself and genomic methylation reconstruction in cloned embryos. Finally, we found that Dnmt1s removal significantly promoted the demethylation and expression of pluripotent genes in cloned embryos. Taken together, these data suggest that Dnmt1s in donor cells is a critical barrier to somatic cell nuclear transfer mediated DNA methylation reprogramming, impairing the development of cloned embryos.

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