The serine 106 residue within the N-terminal transactivation domain is crucial for Oct4 function in mice
The serine 106 residue within the N-terminal transactivation domain is crucial for Oct4 function in mice
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N 端反式激活结构域内的丝氨酸 106 残基对于小鼠中的 Oct4 功能至关重要
DOI：
10.1017/s0967199417000053
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发表时间：
2017
期刊：
影响因子：
1.7
通讯作者：
Akutsu H
中科院分区：
文献类型：
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作者：
Mitani A;Fukuda A;Miyashita T;Umezawa A;Akutsu H
Pou 5 f1/Oct 4是诱导小鼠植入前胚胎多能性和全能性的关键转录因子。在小鼠中，功能丧失或获得实验已证明Oct 4在着床前和发育能力中发挥重要作用。在这项研究中，使用小鼠植入前胚胎作为模型的Oct 4功能的评估，我们构建Oct 4过表达胚胎与各种突变的N-末端反式激活结构域。发育能力和分子生物学表型取决于突变的类型。用丙氨酸替换丝氨酸106导致与野生型Oct 4相似的更严重的表型，表明使用丙氨酸的这种改变对于Oct 4功能是可忽略的。相反，我们发现Oct 4特异性抗体不能识别Oct 4蛋白，当该残基被天冬氨酸取代时（Oct 4-S106 D）。Oct 4-S106 D过表达的胚胎没有表现出发育停滞和异常的染色质结构。因此，这些结果表明，Ser-106残基的N-末端的反式激活结构域是至关重要的Oct 4的功能，并建议该突变可能会影响Oct 4蛋白的构象。
Pou5f1/Oct4 is a key transcription factor for the induction of pluripotency and totipotency in preimplantation mouse embryos. In mice, loss or gain of function experiments have demonstrated an important role for Oct4 in preimplantation and developmental ability. In this study, using mouse preimplantation embryos as a model for the evaluation of Oct4 function, we constructed Oct4 overexpression embryos with various mutations at the N-terminal transactivation domain. Developmental competency and molecular biological phenotypes depended on the type of mutation. The replacement of serine 106 with alanine resulted in more severe phenotypes similar to that of wild type Oct4, indicating that this alteration using alanine is negligible for Oct4 function. In contrast, we found that Oct4-specific antibodies could not recognize Oct4 protein when this residue was replaced by aspartic acid (Oct4-S106D). Oct4-S106D overexpressing embryos did not show developmental arrest and aberrant chromatin structure. Thus, these results demonstrated that the Ser-106 residue within the N-terminal transactivation domain is crucial for Oct4 function and suggested that this mutation might affect Oct4 protein conformation.
影响因子：
21.3
作者：
通讯作者：
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