Evidence map›Paper›PMID 33850123›Full record

ArticleNature communications2021

Mediator subunit Med15 dictates the conserved "fuzzy" binding mechanism of yeast transcription activators Gal4 and Gcn4.

Lisa M Tuttle, Derek Pacheco, Linda Warfield, Damien B Wilburn, Steven Hahn, Rachel E Klevit

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
3.9field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

34 citing papers in PubMed, 62 citations in OpenAlex.

  1. Review
  2. Article
  3. The molecular basis of transcription initiation by RNA polymerase II.Nature reviews. Molecular cell biology · 2026
    Review
  4. Article
  5. Current Challenges of Transcription Compartmentalization Research.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. How proteins sense their cellular environment.Nature reviews. Molecular cell biology · 2025
    Article
  17. Article
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 2 countries.

Lisa M TuttleDivision of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.ORCID 0000-0001-8889-232X
Derek PachecoDivision of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Linda WarfieldDivision of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Damien B WilburnDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
Steven HahnDivision of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. shahn@fredhutch.org.ORCID 0000-0001-7240-2533
Rachel E KlevitDepartment of Biochemistry, University of Washington, Seattle, WA, USA. klevit@u.washington.edu.ORCID 0000-0002-3476-969X
University of Washington · USFred Hutch Cancer Center · USCape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa · ZA

Funding

Mechanisms of eukaryotic transcription activationR01GM075114 · NIGMS · FRED HUTCHINSON CANCER RESEARCH CENTER · PI HAHN, STEVEN M · 2005 to 2020
$7.9M
NIGMS NIH HHS R01 GM075114
6 · The paper itself

Abstract

The acidic activation domain (AD) of yeast transcription factor Gal4 plays a dual role in transcription repression and activation through binding to Gal80 repressor and Mediator subunit Med15. The activation function of Gal4 arises from two hydrophobic regions within the 40-residue AD. We show by NMR that each AD region binds the Mediator subunit Med15 using a "fuzzy" protein interface. Remarkably, comparison of chemical shift perturbations shows that Gal4 and Gcn4, two intrinsically disordered ADs of different sequence, interact nearly identically with Med15. The finding that two ADs of different sequence use an identical fuzzy binding mechanism shows a common sequence-independent mechanism for AD-Mediator binding, similar to interactions within a hydrophobic cloud. In contrast, the same region of Gal4 AD interacts strongly with Gal80 via a distinct structured complex, implying that the structured binding partner of an intrinsically disordered protein dictates the type of protein-protein interaction.

Indexed as

Basic-Leucine Zipper Transcription FactorsDNA-Binding ProteinsMediator ComplexMethyltransferasesModels, MolecularProtein Interaction Domains and MotifsRepressor ProteinsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsTranscription FactorsBasic-Leucine Zipper Transcription FactorsDNA-Binding ProteinsGAL11 protein, S cerevisiaeGAL4 protein, S cerevisiaeGAL80 protein, S cerevisiaeGCN4 protein, S cerevisiaeMediator ComplexMethyltransferasesmRNA (guanine(N7))-methyltransferaseRepressor ProteinsSaccharomyces cerevisiae ProteinsTranscription Factors

Identifiers

PMID33850123
PMCPMC8044209
OpenAlexW3155706022

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.