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从结构到分子凝聚物:中介体功能的新出现机制

From structure to molecular condensates: emerging mechanisms for Mediator function.

作者信息

Lambert Élie, Puwakdandawa Kavindu, Tao Yi Fei, Robert François

机构信息

Institut de recherches cliniques de Montréal, Canada.

Département de Médecine, Faculté de Médecine, Université de Montréal, Canada.

出版信息

FEBS J. 2023 Jan;290(2):286-309. doi: 10.1111/febs.16250. Epub 2021 Nov 11.

DOI:10.1111/febs.16250
PMID:34698446
Abstract

Mediator is a large modular protein assembly whose function as a coactivator of transcription is conserved in all eukaryotes. The Mediator complex can integrate and relay signals from gene-specific activators bound at enhancers to activate the general transcription machinery located at promoters. It has thus been described as a bridge between these elements during initiation of transcription. Here, we review recent studies on Mediator relating to its structure, gene specificity and general requirement, roles in chromatin architecture as well as novel concepts involving phase separation and transcriptional bursting. We revisit the mechanism of action of Mediator and ultimately put forward models for its mode of action in gene activation.

摘要

中介体是一种大型模块化蛋白质组装体,其作为转录共激活因子的功能在所有真核生物中都是保守的。中介体复合物可以整合并传递来自结合在增强子上的基因特异性激活因子的信号,以激活位于启动子处的通用转录机制。因此,它被描述为转录起始过程中这些元件之间的桥梁。在这里,我们综述了关于中介体的最新研究,这些研究涉及其结构、基因特异性和一般要求、在染色质结构中的作用以及涉及相分离和转录爆发的新概念。我们重新审视了中介体的作用机制,并最终提出了其在基因激活中的作用模式模型。

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From structure to molecular condensates: emerging mechanisms for Mediator function.从结构到分子凝聚物:中介体功能的新出现机制
FEBS J. 2023 Jan;290(2):286-309. doi: 10.1111/febs.16250. Epub 2021 Nov 11.
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Transcription regulation by the Mediator complex.中介复合物的转录调控。
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Mediator Roles Going Beyond Transcription.调解人角色超越转录。
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Mechanisms of Mediator complex action in transcriptional activation.中介复合物在转录激活中的作用机制。
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Mediator and cohesin connect gene expression and chromatin architecture.中介体和黏合蛋白连接基因表达和染色质结构。
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Differential regulation during development, aging, and disease implies heart cell specific functions of the Mediator Complex.在发育、衰老和疾病过程中的差异调节意味着中介复合体具有心脏细胞特异性功能。
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The CDK8 kinase module: A novel player in the transcription of translation initiation and ribosomal genes.细胞周期蛋白依赖性激酶8激酶模块:翻译起始和核糖体基因转录中的新角色。
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Enhancer selectivity in space and time: from enhancer-promoter interactions to promoter activation.增强子在时空上的选择性:从增强子-启动子相互作用到启动子激活。
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MED19 encodes two unique protein isoforms that confer prostate cancer growth under low androgen through distinct gene expression programs.MED19 编码两种独特的蛋白异构体,通过不同的基因表达程序在低雄激素条件下促进前列腺癌生长。
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CDK8 and CDK19: positive regulators of signal-induced transcription and negative regulators of Mediator complex proteins.CDK8 和 CDK19:信号诱导转录的正调控因子和 Mediator 复合物蛋白的负调控因子。
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