Overexpression of Tet3 in donor cells enhances goat somatic cell nuclear transfer efficiency
Overexpression of Tet3 in donor cells enhances goat somatic cell nuclear transfer efficiency
复制标题
Tet3在供体细胞中的过度表达提高了山羊体细胞核移植效率
DOI：
10.1111/febs.14515
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发表时间：
2018-07-01
期刊：
影响因子：
5.4
通讯作者：
Zhang, Yong
中科院分区：
文献类型：
--
作者：
Han, Chengquan;Deng, Ruizhi;Zhang, Yong
TET 3在小鼠胚胎发育过程中介导父方基因组的主动DNA去甲基化。然而，山羊胚胎DNA去甲基化的机制仍不清楚。此外，在体细胞核移植（SCNT）克隆的胚胎中也存在异常的DNA甲基化重编程。在本研究中，我们报道了TET 3是山羊植入前胚胎DNA去甲基化的关键因子。Tet 3的敲低阻碍了山羊胚胎中2 - 4细胞阶段的DNA去甲基化，并降低了囊胚中Nanog的表达。Tet 3在体细胞中的过表达可以启动DNA去甲基化，降低5-甲基胞嘧啶水平，增加5-羟甲基胞嘧啶水平，促进关键多能性基因的表达。SCNT后，Tet 3在供体细胞中的过表达纠正了克隆胚胎DNA的异常甲基化，并显著提高了体外和体内发育率（P
Ten-eleven translocation 3 (TET3) mediates active DNA demethylation of paternal genomes during mouse embryonic development. However, the mechanism of DNA demethylation in goat embryos remains unknown. In addition, aberrant DNA methylation reprogramming prevalently occurs in embryos cloned by somatic cell nuclear transfer (SCNT). In this study, we reported that TET3 is a key factor in DNA demethylation in goat pre-implantation embryos. Knockdown of Tet3 hindered DNA demethylation at the two- to four-cell stage in goat embryos and decreased Nanog expression in blastocysts. Overexpression of Tet3 in somatic cells can initiate DNA demethylation, reduce 5-methylcytosine level, increase 5-hydroxymethylcytosine level and promote the expression of key pluripotency genes. After SCNT, overexpression of Tet3 in donor cells corrected abnormal DNA hypermethylation of cloned embryos and significantly enhanced invitro and invivo developmental rate (P