Epigenetic modification agents improve genomic methylation reprogramming in porcine cloned embryos.
Epigenetic modification agents improve genomic methylation reprogramming in porcine cloned embryos.
复制标题
表观遗传修饰剂可改善猪克隆胚胎中的基因组甲基化重编程。
DOI：
10.1262/jrd.2014-062
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
He HB
中科院分区：
文献类型：
--
作者：
Huan YJ;Zhu J;Wang HM;Wu ZF;Zhang JG;Xie BT;Li JY;Kong QR;Liu ZH;He HB
克隆胚胎中不完全的DNA甲基化重编程导致克隆效率低下。我们前期的研究表明，表观遗传修饰剂5-aza-dC或TSA可以提高猪克隆胚胎的发育能力。在这里，我们研究了猪早期胚胎发育过程中基因组甲基化动态和特定基因表达水平。在本研究中，我们的研究结果表明，有一个典型的去甲基化和着丝粒卫星重复序列（CenRep）在受精胚胎的DNA去甲基化和再甲基化的浪潮，而在克隆胚胎，延迟去甲基化和缺乏再甲基化观察。当用5-aza-dC或TSA处理克隆胚胎时，CenRep甲基化重编程得到改善，这与在受精胚胎中检测到的相似。此外，我们发现表观遗传修饰剂，特别是TSA，有效地促进了猪克隆胚胎中组织特异性基因的沉默和早期胚胎发育相关基因的转录。结果表明，表观遗传修饰剂5-aza-dC或TSA可以提高猪克隆胚胎的基因组甲基化重编程，并调节与早期胚胎发育相关基因的适当表达水平，从而获得较高的发育能力。
Incomplete DNA methylation reprogramming in cloned embryos leads to low cloning efficiency. Our previous studies showed that the epigenetic modification agents 5-aza-2’-deoxycytidine (5-aza-dC) or trichostatin A (TSA) could enhance the developmental competence of porcine cloned embryos. Here, we investigated genomic methylation dynamics and specific gene expression levels during early embryonic development in pigs. In this study, our results showed that there was a typical wave of DNA demethylation and remethylation of centromeric satellite repeat (CenRep) in fertilized embryos, whereas in cloned embryos, delayed demethylation and a lack of remethylation were observed. When cloned embryos were treated with 5-aza-dC or TSA, CenRep methylation reprogramming was improved, and this was similar to that detected in fertilized counterparts. Furthermore, we found that the epigenetic modification agents, especially TSA, effectively promoted silencing of tissue specific genes and transcription of early embryo development-related genes in porcine cloned embryos. In conclusion, our results showed that the epigenetic modification agent 5-aza-dC or TSA could improve genomic methylation reprogramming in porcine cloned embryos and regulate the appropriate expression levels of genes related to early embryonic development, thereby resulting in high developmental competence.
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