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后生动物中介体共激活复合物作为转录调控的整合中心。

The metazoan Mediator co-activator complex as an integrative hub for transcriptional regulation.

机构信息

Laboratory of Biochemistry and Molecular Biology, Rockefeller University, 1230 York Avenue, New York, New York 10065, USA.

出版信息

Nat Rev Genet. 2010 Nov;11(11):761-72. doi: 10.1038/nrg2901. Epub 2010 Oct 13.

DOI:10.1038/nrg2901
PMID:20940737
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3217725/
Abstract

The Mediator is an evolutionarily conserved, multiprotein complex that is a key regulator of protein-coding genes. In metazoan cells, multiple pathways that are responsible for homeostasis, cell growth and differentiation converge on the Mediator through transcriptional activators and repressors that target one or more of the almost 30 subunits of this complex. Besides interacting directly with RNA polymerase II, Mediator has multiple functions and can interact with and coordinate the action of numerous other co-activators and co-repressors, including those acting at the level of chromatin. These interactions ultimately allow the Mediator to deliver outputs that range from maximal activation of genes to modulation of basal transcription to long-term epigenetic silencing.

摘要

中介体是一个进化上保守的、多蛋白复合物,是蛋白质编码基因的关键调节因子。在后生动物细胞中,负责维持体内平衡、细胞生长和分化的多条途径通过转录激活因子和抑制因子汇聚到中介体上,这些转录激活因子和抑制因子靶向该复合物的几乎 30 个亚基中的一个或多个。除了与 RNA 聚合酶 II 直接相互作用外,中介体还具有多种功能,可以与众多其他共激活因子和共抑制因子相互作用并协调它们的作用,包括那些在染色质水平上发挥作用的因子。这些相互作用最终使中介体能够传递从基因的最大激活到基础转录的调节再到长期表观遗传沉默的各种输出。

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本文引用的文献

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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。
Nature. 2010 Sep 23;467(7314):430-5. doi: 10.1038/nature09380. Epub 2010 Aug 18.
2
ATAC and Mediator coactivators form a stable complex and regulate a set of non-coding RNA genes.ATAC 和 Mediator 共激活因子形成一个稳定的复合物,并调节一组非编码 RNA 基因。
EMBO Rep. 2010 Jul;11(7):541-7. doi: 10.1038/embor.2010.75. Epub 2010 May 28.
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p53 activates transcription by directing structural shifts in Mediator.p53 通过指导中介体的结构重排来激活转录。
Cell Discov. 2025 Aug 19;11(1):69. doi: 10.1038/s41421-025-00820-1.
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Regulation of inflammatory responses by pH-dependent transcriptional condensates.pH 依赖性转录凝聚物对炎症反应的调控
Cell. 2025 Jul 12. doi: 10.1016/j.cell.2025.06.033.
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Insights into Noncanonical and Diversified Functions of ABCF1: From Health to Disease.ABCF1的非规范和多样化功能洞察:从健康到疾病
J Mol Biol. 2025 Jun 11;437(17):169286. doi: 10.1016/j.jmb.2025.169286.
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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。
J Mol Cell Cardiol Plus. 2025 May 22;12:100456. doi: 10.1016/j.jmccpl.2025.100456. eCollection 2025 Jun.
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MUC1-C dependency in drug resistant HR+/HER2- breast cancer identifies a new target for antibody-drug conjugate treatment.耐药性 HR+/HER2- 乳腺癌中 MUC1-C 的依赖性确定了抗体药物偶联物治疗的新靶点。
NPJ Breast Cancer. 2025 Apr 26;11(1):39. doi: 10.1038/s41523-025-00751-w.
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iScience. 2025 Feb 13;28(4):112017. doi: 10.1016/j.isci.2025.112017. eCollection 2025 Apr 18.
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TBP2 is essential for germ cell development by regulating transcription and chromatin condensation in the oocyte.TBP2通过调节卵母细胞中的转录和染色质凝聚,对生殖细胞发育至关重要。
Genes Dev. 2009 Sep 15;23(18):2210-23. doi: 10.1101/gad.535209.