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A mediator required for activation of RNA polymerase II transcription in vitro

Flanagan, Peter M., Kelleher, Raymond J., Sayre, Michael H., Tschochner, Herbert, Kornberg, Roger D.·1991·Nature

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Abstract

Activator proteins bind to enhancer DNA elements and stimulate the initiation of transcription. It has been proposed that activators contact general initiation factors at a promoter, and evidence for such direct interaction has been obtained. Studies of transcription in vitro, however, have suggested that activators might function through an intermediary molecule(s) distinct from the general factors. In the first of these studies, we exploited the finding that one activator could inhibit transcription stimulated by a second activator (activator interference or 'squelching'). This inhibition, which is attributed to competition between the activators for a common target factor, could not be relieved by addition of a large excess of general initiation factors, suggesting that the target for which activators compete is distinct from these factors. Similar conclusions came from the observation that TFIID's expressed from cloned genes fail to replace partially purified 'natural' TFIID fractions in supporting activation, evidently because they lacked some component present in the impure fractions. While these lines of evidence for a novel 'mediator' of activation were negative, we also showed that a partially purified fraction from yeast would reverse activator interference. This positive effect of a presumptive mediator provided an assay for its activity, but its role in activation was still only inferred. We now present direct evidence for a mediator which is required for stimulation of transcription in vitro by the activators GAL4-VP16 and GCN4, but which has no effect on transcription in the absence of activator protein.

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“Parallel studies with Saccharomyces cerevisiae revealed the existence of a coactivator or Mediator (8) that interacts with Pol II to form a Pol II holoenzyme (19, 44) and that consists of genetically identified SRB and”
Background
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Background
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BackgroundMethodInfluential
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The Nuclear Pore-Associated TREX-2 Complex Employs Mediator to Regulate Gene Expression
Schneider, M., Hellerschmied, D., Schubert, T., Amlacher, S., Vinayachandran, V., Reja, R., Pugh, B. F., Clausen, T., & Köhler, A. (2015) · Cell · doi:10.1016/j.cell.2015.07.059 · Cited by 125
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An endoribonuclease-based feedforward controller for decoupling resource-limited genetic modules in mammalian cells
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Background
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REF4 and RFR1, Subunits of the Transcriptional Coregulatory Complex Mediator, Are Required for Phenylpropanoid Homeostasis in Arabidopsis*
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Background
Mediator Structural Conservation and Implications for the Regulation Mechanism
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Background
Mediator Head module structure and functional interactions
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Background
pX, the HBV‐encoded coactivator, interacts with components of the transcription machinery and stimulates transcription in a TAF‐independent manner.
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BackgroundMethodInfluential
The VP16 transcription activation domain is functional when targeted to a promoter-proximal RNA sequence.Preprint
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Background
Diverse roles of the Mediator complex in plants
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“Furthermore, a number of SWI/SNF subunits, including Swi3, Swi5, and SWI2/SNF2 ATPase, have been identified as being stably associated subunits of the RNAPolymerase-II-mediator complex, an interface between specific regulatory proteins and the general transcription machinery of eukaryotes (Flanagan et al. 1991; Kim et…”
Background

Authors: Flanagan, P. M., Kelleher, R. J., Sayre, M. H., Tschochner, H., & Kornberg, R. D.
Affiliations: Stanford Medicine (US)
ORCID: Tschochner, Herbert
Kornberg, Roger D.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 1991-04
Volume: 350
Issue: 6317
Pages: 436-438
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/350436a0
OpenAlex: W2062439115
Cited by: 386
References: 0
Citations by year: 2026: 1 · 2025: 8 · 2024: 9 · 2023: 3 · 2022: 10 · 2021: 13 · 2020: 21 · 2019: 11 · 2018: 9 · 2017: 11 · 2016: 11 · 2015: 8 · 2014: 5 · 2013: 15 · 2012: 9
FWCI: 11.51
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords: RNA polymerase II transcription, transcriptional activator, Mediator complex, TFIID, GAL4-VP16, GCN4, enhancers, transcriptional activation, yeast
MeSH terms: DNA-Binding Proteins, Enzyme Activation, Fungal Proteins, Nuclear Proteins, Recombinant Proteins, RNA Polymerase II, Saccharomyces cerevisiae, Transcription Factors, Transcription, Genetic, Saccharomyces cerevisiae Proteins, Transcription Factor TFIID, In Vitro Techniques

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A mediator required for activation of RNA polymerase II transcription in vitro

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