The cyclin-dependent kinase 1 (Cdk1) drives cell division. To uncover additional functions of Cdk1, we generated knockin mice expressing an analog-sensitive version of Cdk1 in place of wild-type Cdk1. In our study, we focused on embryonic stem cells (ESCs), because this cell type displays particularly high Cdk1 activity. We found that in ESCs, a large fraction of Cdk1 substrates is localized on chromatin. Cdk1 phosphorylates many proteins involved in epigenetic regulation, including writers and erasers of all major histone marks. Consistent with these findings, inhibition of Cdk1 altered histone-modification status of ESCs. High levels of Cdk1 in ESCs phosphorylate and partially inactivate Dot1l, the H3K79 methyltransferase responsible for placing activating marks on gene bodies. Decrease of Cdk1 activity during ESC differentiation de-represses Dot1l, thereby allowing coordinated expression of differentiation genes. These analyses indicate that Cdk1 functions to maintain the epigenetic identity of ESCs.

中文翻译：

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Cdk1控制胚胎干细胞中的全局表观遗传景观。

细胞周期蛋白依赖性激酶1（Cdk1）驱动细胞分裂。为了揭示Cdk1的其他功能，我们生成了敲除表达野生型Cdk1的Cdk1类似敏感版本的小鼠。在我们的研究中，我们专注于胚胎干细胞（ESC），因为这种细胞类型显示出特别高的Cdk1活性。我们发现在ESC中，大部分Cdk1底物位于染色质上。Cdk1磷酸化许多参与表观遗传调控的蛋白质，包括所有主要组蛋白标记的书写者和擦除者。与这些发现一致，抑制Cdk1改变了ESCs的组蛋白修饰状态。ESC中高水平的Cdk1磷酸化并使Dot11部分失活，Dot11是负责在基因体上放置激活标记的H3K79甲基转移酶。在ESC分化过程中Cdk1活性的降低会抑制Dot11，从而使分化基因得以协调表达。这些分析表明Cdk1的功能是维持ESC的表观遗传身份。