Dynamic reprogramming of histone acetylation and methylation in the first cell cycle of cloned mouse embryos
Dynamic reprogramming of histone acetylation and methylation in the first cell cycle of cloned mouse embryos
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DOI：
10.1095/biolreprod.107.063149
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发表时间：
2007-12-01
影响因子：
3.6
通讯作者：
Gao, Shaorong
中科院分区：
文献类型：
--
作者：
Wang, Fengchao;Kou, Zhaohui;Gao, Shaorong
表观遗传重编程被认为在体细胞核移植（SCNT）重建的克隆胚胎发育中起重要作用。在本研究中，动态重编程组蛋白乙酰化和甲基化修饰的克隆胚胎的第一个细胞周期进行了调查。我们的研究结果表明，部分体细胞遗传的赖氨酸乙酰化的核心组蛋白（H3K9，H3K14，H4K16）可以快速脱乙酰化SCNT后，并发生再乙酰化激活处理。然而，核心组蛋白上的其他赖氨酸残基（H4K8，H4K12）的乙酰化标记在克隆胚胎的基因组中持续存在，仅在SCNT和激活处理过程中发生轻度脱乙酰化。通过这两种不同的程序，体细胞克隆胚胎建立了类似于胞质内单精子注射产生的正常胚胎中的组蛋白乙酰化修饰。此外，用组蛋白去乙酰化酶抑制剂曲古抑菌素A（TSA）处理克隆胚胎，以类似于正常胚胎的方式改善了组蛋白乙酰化，TSA处理的克隆胚胎中组蛋白乙酰化的改善可能有助于TSA处理克隆的发育改善。与受精胚胎的亲本基因组中存在的不对称组蛋白H3K9三甲基化和二甲基化相反，H3K9的三甲基化和二甲基化在克隆胚胎中逐渐去甲基化，并且这种组蛋白H3K9去甲基化可能对克隆胚胎的基因激活至关重要。总之，我们的研究结果表明，在克隆胚胎中组蛋白乙酰化和甲基化修饰的动态重编程是发育调节的。
Epigenetic reprogramming is thought to play an important role in the development of cloned embryos reconstructed by somatic cell nuclear transfer (SCNT). In the present study, dynamic reprogramming of histone acetylation and methylation modifications was investigated in the first cell cycle of cloned embryos. Our results demonstrated that part of somatic inherited lysine acetylation on core histones (H3K9, H3K14, H4K16) could be quickly deacetylated following SCNT, and reacetylation occurred following activation treatment. However, acetylation marks of the other lysine residues on core histones (H4K8, H4K12) persisted in the genome of cloned embryos with only mild deacetylation occurring in the process of SCNT and activation treatment. The somatic cloned embryos established histone acetylation modifications resembling those in normal embryos produced by intracytoplasmic sperm injection through these two different programs. Moreover, treatment of cloned embryos with a histone deacetylase inhibitor, Trichostatin A (TSA), improved the histone acetylation in a manner similar to that in normal embryos, and the improved histone acetylation in cloned embryos treated with TSA might contribute to improved development of TSA-treated clones. In contrast to the asymmetric histone H3K9 tri- and dimethylation present in the parental genomes of fertilized embryos, the tri- and dimethylations of H3K9 were gradually demethylated in the cloned embryos, and this histone H3K9 demethylation may be crucial for gene activation of cloned embryos. Together, our results indicate that dynamic reprogramming of histone acetylation and methylation modifications in cloned embryos is developmentally regulated.