Convergence of Stress‐Induced Hormone Signaling Pathways on a Transcriptional Co‐Factor
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Mediator is a massive and flexible complex involved in eukaryotic gene regulation. Basically, it acts as a bridge between a transcription factor and transcriptional machinery. However, latest reports suggest that Mediator is involved in almost all the aspects of gene transcription including initiation of transcription, elongation of transcript, splicing of transcript, gene looping, and termination of transcription. The Mediator complex consists of several subunits, which are arranged in different modules named Head, Middle, Tail, and Kinase. Few subunits have not yet been assigned to any module. In Arabidopsis, it seems that different compositions of subunits might form functional complexes in different contexts and scenarios as different stresses and phytohormones affect transcript abundance of specific set of these subunit genes. Although the Mediator complex is required in the basic mechanism of transcription initiation and regulation of almost all the class II genes, several individual subunits have been found to be important in specific transcriptional responses. In this chapter, we discuss involvement of Mediator subunits in stress responses. Since hormones play an important role in stress responses, we explain the known and probable involvement of Mediator in phytohormone mediated transcriptional responses evoked by different biotic and abiotic stresses in plants.Keywords:
Mediator
Transcription
RNA polymerase II
Eukaryotic transcription
Mediator
RNA polymerase II
Transcription preinitiation complex
General transcription factor
Transcription
Eukaryotic transcription
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In eukaryotic cells from yeast to humans, the multi‐subunit Mediator complex contributes to transcriptional regulation of RNA polymerase II (Pol II) by acting as a coregulator. The Mediator regulates multiple stages of transcription by interacting with gene‐specific transcription factors, Pol II, and factors that regulate Pol II initiation and elongation. Mediator also affects the activities of factors involved in mRNA processing and chromatin regulation. Because of its central role in transcription, Mediator modulates pathways linked to cell differentiation, cell growth, and tissue development. Metazoan Mediator is composed of over 30 subunits in organized into several modules. In metazoa, Mediator core, composed of head, middle, and tail modules, can interact with a dissociable subunit called MED26. When isolated from cells, a large fraction of MED26‐containing Mediator is associated with Pol II; however, it remains unclear whether or how MED26 contributes to the Mediator‐Pol II interaction. A second form of Mediator lacks MED26 and instead binds a dissociable kinase module containing one of two kinase‐cyclin pairs, CDK8/Cyclin C or CDK19/Cyclin C. Because kinase module interferes with binding of the Mediator core to Pol II, it was proposed that Mediator associated with kinase module might function as a repressive cofactor; however, more recent results from multiple labs supports the model that both MED26‐Mediator and kinase module‐associated Mediator contribute to gene activation. A major focus of our research is to understand how these two forms of Mediator are involved in transcription regulation. Ongoing experiments seek to explore mechanisms that regulate Mediator‐Pol II interactions. In particular, we wish to understand (i) how Mediator recognizes Pol II and how the Mediator‐Pol II interaction is maintained, (ii) how Mediator is released from Pol II after transcription initiation, and (iii) whether and how the kinase module and MED26 contribute to each of these processes. Support or Funding Information The Stowers Institute for Medical ResearchThe Helen Nelson Medical Research Fund at Greater Kansas City Community Foundation
Mediator
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Cyclin-dependent kinase 8
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RNA polymerase II (Pol II), whose 12 subunits are conserved across eukaryotes, is at the heart of the machinery responsible for transcription of mRNA. Although associated general transcription factors impart promoter specificity, responsiveness to gene- and tissue-selective activators additionally depends on the multiprotein Mediator coactivator complex. We have isolated from tissue extracts a distinct and abundant mammalian Pol II subpopulation that contains an additional tightly associated polypeptide, Gdown1. Our results establish that Gdown1-containing Pol II, designated Pol II(G), is selectively dependent on and responsive to Mediator. Thus, in an in vitro assay with general transcription factors, Pol II lacking Gdown1 displays unfettered levels of activator-dependent transcription in the presence or absence of Mediator. In contrast, Pol II(G) is dramatically less efficient in responding to activators in the absence of Mediator yet is highly and efficiently responsive to activators in the presence of Mediator. Our results reveal a transcriptional control mechanism in which Mediator-dependent regulation is enforced by means of Gdown1, which likely restricts Pol II function only to be reversed by Mediator.
Mediator
RNA polymerase II
Transcription
General transcription factor
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Mediator
RNA polymerase II
Transcription preinitiation complex
Enhancer RNAs
Transcription
General transcription factor
Eukaryotic transcription
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Mediator
RNA polymerase II
General transcription factor
Transcription preinitiation complex
Transcription
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Recent advances in cryo-electron microscopy have led to multiple structures of Mediator in complex with the RNA polymerase II (Pol II) transcription initiation machinery. As a result we now hold in hands near-complete structures of both yeast and human Mediator complexes and have a better understanding of their interactions with the Pol II pre-initiation complex (PIC). Herein, we provide a summary of recent achievements and discuss their implications for future studies of Mediator and its role in gene regulation.
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RNA polymerase II
Transcription
Transcription preinitiation complex
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Abstract The Mediator complex functions in eukaryotic transcription by stimulating the cooperative assembly of a pre-initiation complex (PIC) and recruitment of RNA Polymerase II (Pol II) for gene activation. The core Mediator complex is organized into head, middle, and tail modules, and in budding yeast ( Saccharomyces cerevisiae ), Mediator recruitment has generally been ascribed to sequence-specific activators engaging the tail module triad of Med2-Med3-Med15 at upstream activating sequences (UASs). We show that med2 Δ med3 Δ med15 Δ yeast are viable and that Mediator lacking Med2-Med3-Med15 is associated with active promoters genome-wide. To test whether Mediator might alternatively be recruited via interactions with the PIC, we examined Mediator association genome-wide after depleting PIC components. We found that depletion of Taf1, Rpb3, and TBP profoundly affected Mediator association at active gene promoters, with TBP being critical for transit of Mediator from UAS to promoter, while Pol II and Taf1 stabilize Mediator association at proximal promoters.
Mediator
RNA polymerase II
Transcription
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Mediator
RNA polymerase II
Transcription
General transcription factor
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Mediator
RNA polymerase II
Transcription
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Mediator
RNA polymerase II
CTD
Transcription
Cyclin-dependent kinase 8
Eukaryotic transcription
Specificity factor
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