Additional file 3: of The Mediator complex subunits MED25/PFT1 and MED8 are required for transcriptional responses to changes in cell wall arabinose composition and glucose treatment in Arabidopsis thaliana
Mathilde Séguéla-ArnaudCaroline SmithMarcos CastellanosSean MayHarry FischlNeil McKenzieMichael W. Bevan
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ANOVA tables of gene expression in dark grown seedlings of Col, hsr8-1 , hsr8-1pft1-2 and pft1-2 . (XLS 68Â kb)Keywords:
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Arabinose
Abstract DNA-binding transcription factors (TFs) remain challenging to target with molecular probes. Many TFs function in part through interaction with Mediator; we sought to block p53 function by disrupting the p53-Mediator interaction. Through rational design and activity-based screening, we characterized a stapled peptide, with functional mimics of both p53 activation domains, that selectively inhibited p53- and Mediator-dependent transcription in vitro . This “bivalent peptide” also suppressed p53 transcriptional response in human cancer cells. Our strategy circumvents the TF and instead targets the TF-Mediator interface, with desired transcriptional outcomes. Different TFs target Mediator through different subunits, suggesting this strategy could be broadly applied.
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During the development of the mammalian cardiovascular system, the formation of a mature and fully functional cardiovascular system needs the fine coordination of the morphogenesis of various molecules, cells, tissues, and organs. Abnormalities in these processes usually lead to serious congenital heart defects. The determination and maintenance of cell fate in multicellular organisms depend to a large extent on the precise timing and control of RNA polymerase II (Pol II) transcription, and the transcription Mediator complex plays an irreplaceable role in the Pol II transcription process. Mediator is an evolutionarily conserved multi-subunit protein complex, including four parts: head, middle, tail, and kinase. It is a functional bridge between transcription factors and basic transcription machines. In recent years, due to the key role of Mediator in the transcriptional regulation of gene expression, many of human heart diseases have been confirmed to be related to specific Mediator gene mutations, such as heart valve defects, translocation of the great arteries, DiGeorge syndrome and some cardiovascular diseases related to energy homeostasis. In this review, we summarize the role of Mediator in cardiovascular development and disease, focusing on the role of Mediator in the development of cardiovascular disease, and provides a broad idea for the research on Mediator-related cardiovascular system development and diseases.哺乳动物心血管系统发育过程中,各分子、细胞和组织器官形态发生过程的精细协调对于形成成熟且功能齐全的心血管系统是不可或缺的,这些过程出现异常通常会导致严重的先天性心血管发育缺陷。多细胞生物中细胞命运的决定和维持在很大程度上依赖于对RNA聚合酶II (Pol II)转录活性的时空精确调控,而转录中介体(Mediator)在Pol II转录过程中起着重要的协同作用。Mediator是一种进化上保守的多亚基蛋白质复合体,包括头部、中部、尾部和激酶部四个部分,是转录因子和基础转录机器之间的功能联系的桥梁。近年来,鉴于Mediator在基因表达中的关键作用,越来越多的人类心血管疾病被证实与特定的Mediator基因突变相关,如心脏瓣膜缺陷、大动脉转位、DiGeorge综合征及一些与能量稳态失衡相关的心血管疾病。本文就Mediator在心血管系统发育和疾病中的作用进行综述,重点讨论Mediator对转录调控的影响在心血管疾病发生发展中的作用,旨在为与Mediator相关的心血管系统发育和疾病的研究提供广阔的研究思路。.
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Mediator, originally discovered in yeast and composed of multi-subunits with a high molecular mass , is an essential component of the RNA polymerase Ⅱgeneral transcriptional machinery and plays a crucial part in the activation and repression of eukaryotic mRNA synthesis. Regulatory information could be conveyed through changes in Mediator conformation that would influence the transcription initiation process. Recent studies have defined the subunit composition and associated activities of mammalian Mediator, and revealed a striking evolutionary conservation of Mediator structure and function from yeast to man.
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Mediator is a multi-protein complex,which includes at least 25 subunits,forming a link between gene-specific transcription factors and pre-initiation complex.Mediator serves crucial functions in both protein-coding genes and noncoding RNA genes,and plays important roles in plant development and resistance.The phenotypes of individual mediator complex subunit mutants are distinct from each other,suggesting that the deletion of one mediator subunit does not interfere with transcription in general,but instead alters the expression of specific target genes.Therefore,certain developmental process in plant is regulated by specific mediator subunit genes.The clarification of the functions for individual mediator subunits is vital for fully understanding the developmental course and stress response.In this review,we discussed the roles of mediator complex in plant development combined with the new reports about mediator,and dissected the expression profiles of mediator subunits,proposed the assumption and expectation for the future study of mediator in plants.
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