Selective gene expression is crucial in maintaining the self-renewing and multipotent properties of stem cells. Mediator is a large, evolutionarily conserved, multi-subunit protein complex that modulates gene expression by relaying signals from cell type-specific transcription factors to RNA polymerase II. In humans, this complex consists of 30 subunits arranged in four modules. One critical module of the Mediator complex is the kinase module consisting of four subunits: MED12, MED13, CDK8, and CCNC. The kinase module exists in variable association with the 26-subunit Mediator core and affects transcription through phosphorylation of transcription factors and by controlling Mediator structure and function. Many studies have shown the kinase module to be a key player in the maintenance of stem cells that is distinct from a general role in transcription. Genetic studies have revealed that dysregulation of this kinase subunit contributes to the development of many human diseases. In this review, we discuss the importance of the Mediator kinase module by examining how this module functions with the more recently identified transcriptional super-enhancers, how changes in the kinase module and its activity can lead to the development of human disease, and the role of this unique module in directing and maintaining cell state. As we look to use stem cells to understand human development and treat human disease through both cell-based therapies and tissue engineering, we need to remain aware of the on-going research and address critical gaps in knowledge related to the molecular mechanisms that control cell fate.

中文翻译：

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Mediator 的激酶模块：细胞命运的模块化调节器

选择性基因表达对于维持干细胞的自我更新和多能特性至关重要。介质是一种大型的、进化上保守的、多亚基的蛋白质复合物，它通过将信号从细胞类型特异性转录因子传递到 RNA 聚合酶 II 来调节基因表达。在人类中，这个复合体由排列在四个模块中的 30 个亚基组成。Mediator 复合体的一个关键模块是由四个亚基组成的激酶模块：MED12、MED13、CDK8 和 CCNC。激酶模块与 26 个亚基 Mediator 核心以可变关联形式存在，并通过转录因子的磷酸化和控制 Mediator 结构和功能来影响转录。许多研究表明激酶模块是维持干细胞的关键参与者，这与转录中的一般作用不同。遗传研究表明，该激酶亚基的失调会导致许多人类疾病的发展。在这篇综述中，我们通过检查该模块如何与最近发现的转录超级增强子一起发挥作用，激酶模块及其活性的变化如何导致人类疾病的发展，以及其作用来讨论介体激酶模块的重要性。这种独特的模块在指导和维持细胞状态方面的作用。当我们希望使用干细胞通过基于细胞的疗法和组织工程来了解人类发育和治疗人类疾病时，