Auxin-degron system identifies immediate mechanisms of Oct4
Auxin-degron system identifies immediate mechanisms of Oct4
复制标题
生长素-降解决定子系统识别 Oct4 的直接机制
DOI：
10.1101/2020.09.21.306241
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Bates L
中科院分区：
文献类型：
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作者：
Bates L
多能性因子OCT4对于维持体外和体内的原始多能干细胞至关重要。然而，OCT4在这一过程中的具体作用尚不清楚。在这里，我们开发了一个快速蛋白水平的OCT4耗竭系统，证明了OCT4缺失的直接下游反应是关键多能性因子的表达减少。我们的数据表明，OCT4对几种关键多能因子的有效转录是必需的，并表明滋养外胚层标记物的表达是随后的事件。此外，我们发现NANOG能够在没有OCT4的情况下与基因组结合，并且这种结合实际上是增强的。然而，在全球范围内，活性增强子相关的组蛋白标记H3K27ac被耗尽。我们的工作表明，虽然OCT4是维持原始转录因子网络所必需的，但在正常的胚胎干细胞水平上，它通过抑制NANOG结合来拮抗该网络。
The pluripotency factor OCT4 is essential for the maintenance of naive pluripotent stem cellsin vitroandin vivo. However, the specific role of OCT4 in this process remains unknown. Here, we developed a rapid protein-level OCT4 depletion system that demonstrates that the immediate downstream response to loss of OCT4 is reduced expression of key pluripotency factors. Our data show a requirement for OCT4 for the efficient transcription of several key pluripotency factors and suggest that expression of trophectoderm markers is a subsequent event. In addition, we find that NANOG is able to bind to the genome in the absence of OCT4, and this binding is in fact enhanced. Globally, however, the active enhancer-associated histone mark H3K27ac is depleted. Our work establishes that, while OCT4 is required for the maintenance of the naive transcription factor network, at a normal embryonic stem cell levels it antagonizes this network through inhibition of NANOG binding.