Trichostatin A specifically improves the aberrant expression of transcription factor genes in embryos produced by somatic cell nuclear transfer.
Trichostatin A specifically improves the aberrant expression of transcription factor genes in embryos produced by somatic cell nuclear transfer.
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Trichostatin A特异性改善了由体细胞核转移产生的胚胎中转录因子基因的异常表达。
DOI：
10.1038/srep10127
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发表时间：
2015-05-14
影响因子：
4.6
通讯作者：
Ogura A
中科院分区：
文献类型：
--
作者：
Inoue K;Oikawa M;Kamimura S;Ogonuki N;Nakamura T;Nakano T;Abe K;Ogura A
虽然体细胞核移植（SCNT）克隆哺乳动物已在许多物种中建立，但发育效率低，阻碍了其实际应用。用组蛋白去乙酰化酶（HDAC）抑制剂处理SCNT衍生的胚胎可以改善其发育，但其潜在机制仍不清楚。为了解决这个问题，我们分析了SCNT衍生的2-细胞小鼠胚胎的基因表达谱，这些胚胎用一种最适合用于小鼠克隆的有效HDAC抑制剂阿司他丁A（TSA）处理。出乎意料的是，TSA对胚胎中异常表达基因的数量或整体基因表达模式没有影响。然而，通过基因本体和功能分析的深入研究显示，TSA治疗特异性地改善了编码转录因子及其调节因子的一小部分基因的表达，表明它们积极参与从头RNA合成。事实上，将这些转录因子之一Spi-C引入胚胎中至少部分地模拟了TSA通过激活与转录调控相关的基因网络而诱导的胚胎发育改善。因此，TSA处理对胚胎基因表达的影响似乎不是随机的，而是比预期的更特异，靶向指导发育并在2细胞阶段触发合子基因组激活的基因。
Although mammalian cloning by somatic cell nuclear transfer (SCNT) has been established in various species, the low developmental efficiency has hampered its practical applications. Treatment of SCNT-derived embryos with histone deacetylase (HDAC) inhibitors can improve their development, but the underlying mechanism is still unclear. To address this question, we analysed gene expression profiles of SCNT-derived 2-cell mouse embryos treated with trichostatin A (TSA), a potent HDAC inhibitor that is best used for mouse cloning. Unexpectedly, TSA had no effect on the numbers of aberrantly expressed genes or the overall gene expression pattern in the embryos. However, in-depth investigation by gene ontology and functional analyses revealed that TSA treatment specifically improved the expression of a small subset of genes encoding transcription factors and their regulatory factors, suggesting their positive involvement in de novo RNA synthesis. Indeed, introduction of one of such transcription factors, Spi-C, into the embryos at least partially mimicked the TSA-induced improvement in embryonic development by activating gene networks associated with transcriptional regulation. Thus, the effects of TSA treatment on embryonic gene expression did not seem to be stochastic, but more specific than expected, targeting genes that direct development and trigger zygotic genome activation at the 2-cell stage.
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影响因子：
3.6
作者：
Kageyama, SI;Nagata, M;Aoki, F
通讯作者：
Aoki, F
影响因子：
3.6
作者：
Hong-Thuy Bui;Seo, Hyeon-Jeong;Kim, Jin-Hoi
通讯作者：
Kim, Jin-Hoi
影响因子：
3.6
作者：
Inoue, K;Ogonuki, N;Ogura, A
通讯作者：
Ogura, A
影响因子：
64.5
作者：
Matoba S;Liu Y;Lu F;Iwabuchi KA;Shen L;Inoue A;Zhang Y
通讯作者：
Zhang Y
影响因子：
2.7
作者：
Davis, W;Schultz, RM
通讯作者：
Schultz, RM