Structure and Functions of the Mediator Complex

Putlyaev, E. V.; Ibragimov, A. N.; Лебедева, Л. А.; Georgiev, Pavel; Shidlovskii, Yulii V.

doi:10.1134/s0006297918040132

Cited by 6 publications

(6 citation statements)

References 141 publications

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“…The unicellular eukaryote Saccharomyces cerevisiae has a 12.1-Mb genome, and the binding sites of regulators in the enhancer-like UAS [ 3 ] are usually several hundreds of base pairs away from the core promoter, at maximum 1 Kb [ 30 , 31 ]. In this case, the interaction of the activator with general TFs and RNAP requires a loop formation between the enhancer and promoter [ 32 ] and the Mediator complex, a crucial eukaryotic multi-component transcriptional coactivator [ 33 ]. An increase in the distance between the UAS and the core promoter results in loss of function [ 34 ].…”

Section: The Origin Of Transcriptional Enhancers Of Eukaryotes Andmentioning

confidence: 99%

Evolution of Regulated Transcription

Bylino

Ibragimov

Shidlovskii

2020

Cells

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The genomes of all organisms abound with various cis-regulatory elements, which control gene activity. Transcriptional enhancers are a key group of such elements in eukaryotes and are DNA regions that form physical contacts with gene promoters and precisely orchestrate gene expression programs. Here, we follow gradual evolution of this regulatory system and discuss its features in different organisms. In eubacteria, an enhancer-like element is often a single regulatory element, is usually proximal to the core promoter, and is occupied by one or a few activators. Activation of gene expression in archaea is accompanied by the recruitment of an activator to several enhancer-like sites in the upstream promoter region. In eukaryotes, activation of expression is accompanied by the recruitment of activators to multiple enhancers, which may be distant from the core promoter, and the activators act through coactivators. The role of the general DNA architecture in transcription control increases in evolution. As a whole, it can be seen that enhancers of multicellular eukaryotes evolved from the corresponding prototypic enhancer-like regulatory elements with the gradually increasing genome size of organisms.

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Section: The Origin Of Transcriptional Enhancers Of Eukaryotes Andmentioning

confidence: 99%

Evolution of Regulated Transcription

Bylino

Ibragimov

Shidlovskii

2020

Cells

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“…As part of the Mediator complex, the CKM is capable of modulating RNA Pol II-dependent transcription in both a positive and negative manner. Excluding the CKM, the Mediator core structure can be divided into head, middle, and tail domains [17,27,50]. In contrast to the CKM, however, these structural elements are not dissociable and form a single physical unit.…”

Section: The Transcriptional Function Of Cyclin C-dependent Kinasesmentioning

confidence: 99%

“…In order to fulfill its duty as a transcription factor (referred to here as the day job function), cyclin C interacts with Cdk8 as part of a highly conserved multi-protein regulatory complex called Mediator that associates with RNA Pol II [16,17,18]. The complex between transcription factors, Mediator, and the transcription machinery is collectively termed as the RNA polymerase II holoenzyme [19].…”

Section: Introductionmentioning

confidence: 99%

Cyclin C: The Story of a Non-Cycling Cyclin

Ježek

Smethurst

Stieg

et al. 2019

Biology

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The class I cyclin family is a well-studied group of structurally conserved proteins that interact with their associated cyclin-dependent kinases (Cdks) to regulate different stages of cell cycle progression depending on their oscillating expression levels. However, the role of class II cyclins, which primarily act as transcription factors and whose expression remains constant throughout the cell cycle, is less well understood. As a classic example of a transcriptional cyclin, cyclin C forms a regulatory sub-complex with its partner kinase Cdk8 and two accessory subunits Med12 and Med13 called the Cdk8-dependent kinase module (CKM). The CKM reversibly associates with the multi-subunit transcriptional coactivator complex, the Mediator, to modulate RNA polymerase II-dependent transcription. Apart from its transcriptional regulatory function, recent research has revealed a novel signaling role for cyclin C at the mitochondria. Upon oxidative stress, cyclin C leaves the nucleus and directly activates the guanosine 5’-triphosphatase (GTPase) Drp1, or Dnm1 in yeast, to induce mitochondrial fragmentation. Importantly, cyclin C-induced mitochondrial fission was found to increase sensitivity of both mammalian and yeast cells to apoptosis. Here, we review and discuss the biology of cyclin C, focusing mainly on its transcriptional and non-transcriptional roles in tumor promotion or suppression.

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“…К белкам группы Trithorax, проявляющим себя в генетических тестах, относится также Rad21 (RAD21 у млекопитающих) [109] -субъединица когезинового комплекса. Когезиновый комплекс стабилизирует дальние взаимодействия в ядре, в том числе энхансер-промоторные контакты, что необходимо для активации транскрипции [110,111].…”

Section: комплексы группы Trxunclassified

Polycomb and Trithorax Group Proteins: The Long Road from Mutations in Drosophila to Use in Medicine

2020

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Polycomb group (PcG) and Trithorax group (TrxG) proteins are evolutionarily conserved factors responsible for the repression and activation of the transcription of multiple genes in Drosophila and mammals. Disruption of the PcG/TrxG expression is associated with many pathological conditions, including cancer, which makes them suitable targets for diagnosis and therapy in medicine. In this review, we focus on the major PcG and TrxG complexes, the mechanisms of PcG/TrxG action, and their recruitment to chromatin. We discuss the alterations associated with the dysfunction of a number of factors of these groups in oncology and the current strategies used to develop drugs based on small-molecule inhibitors.

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Structure and Functions of the Mediator Complex

Cited by 6 publications

References 141 publications

Evolution of Regulated Transcription

Evolution of Regulated Transcription

Cyclin C: The Story of a Non-Cycling Cyclin

Polycomb and Trithorax Group Proteins: The Long Road from Mutations in Drosophila to Use in Medicine

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