Trichostatin a improves histone acetylation in bovine somatic cell nuclear transfer early embryos
Trichostatin a improves histone acetylation in bovine somatic cell nuclear transfer early embryos
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DOI：
10.1089/clo.2007.0002
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发表时间：
2008-09-01
期刊：
影响因子：
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通讯作者：
Cibelli, Jose B.
中科院分区：
文献类型：
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作者：
Iager, Amy E.;Ragina, Neli P.;Cibelli, Jose B.
表观遗传异常可能妨碍体细胞核移植（SCNT）后正确和完整的核重编程，并可能导致观察到的克隆胚胎活力降低。在本研究中，我们测试了组蛋白去乙酰化酶抑制剂（H：DACi），抑制素A（TSA），对克隆牛植入前胚胎的发育和组蛋白乙酰化的影响。我们的研究结果表明，用50 nM TSA处理活化的重建SCNT胚胎13 h，产生了8细胞胚胎，其组蛋白H4在赖氨酸5处的乙酰化水平（AcH4K5）与受精胚胎相似，显著高于对照NT胚胎（p < 0.005）。此外，TSA处理导致SCNT胚胎具有与受精对应物相似的植入前发育潜力，因为在卵裂率和囊胚率或囊胚总细胞数方面没有观察到差异（p > 0.05）。在单胚泡中测量八个选定的发育重要基因显示出三个处理组之间相似的表达谱，除了Nanog、Cdx 2和DNMT 3b，其在TSA处理的NT中的表达水平高于体外受精（IVF）胚胎。本文提供的数据表明，TSA可以改善早期克隆牛胚胎中的至少一种表观遗传标记。然而，有必要对足月的发育进行评估，以确定这种影响是否反映了发育潜力的真正增加。
Epigenetic aberrancies likely preclude correct and complete nuclear reprogramming following somatic cell nuclear transfer (SCNT), and may underlie the observed reduced viability of cloned embryos. In the present study, we tested the effects of the histone deacetylase inhibitor (H:DACi), trichostatin A (TSA), on development and histone acetylation of cloned bovine preimplantation embryos. Our results indicated that treating activated reconstructed SCNT embryos with 50 nM TSA for 13 h produced eight-cell embryos with levels of acetylation of histone H4 at lysine 5 (AcH4K5) similar to fertilized counterparts and significantly greater than in control NT embryos (p < 0.005). Further, TSA treatment resulted in SCNT embryos with preimplantation developmental potential similar to fertilized counterparts, as no difference was observed in cleavage and blastocyst rates or in blastocyst total cell number (p > 0.05). Measurement of eight selected developmentally important genes in single blastocysts showed a similar expression profile among the three treatment groups, with the exception of Nanog, Cdx2, and DNMT3b, whose expression levels were higher in TSA-treated NT than in to vitro fertilized (IVF) embryos. Data presented herein demonstrate that TSA can improve at least one epigenetic mark in early cloned bovine embryos. However, evaluation of development to full-term is necessary to ascertain whether this effect reflects a true increase in developmental potential.