Evidence map›Paper›PMID 40614721›Full record

ArticleMolecular cell2025

Reconciling competing models on the roles of condensates and soluble complexes in transcription factor function.

Anne Bremer, Walter H Lang, Ryan P Kempen, Kumari Sweta, Aaron B Taylor, Madeleine B Borgia, Aseem Z Ansari, Tanja Mittag

Abstract read
In one paragraph

Article in Molecular cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
–field-weighted citation impact
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

11 citing papers in PubMed.

  1. Review
  2. Article
  3. Nonlinearities and Switch-Like Behavior in Gene Expression: From Genetics to Biochemistry and Back.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Review
  4. Article
  5. The Polymers of Life: Exploring Cellular Function Through Polymer Concepts.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  6. Review
  7. Review
  8. Review
  9. Article
  10. Article
  11. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Anne BremerDepartment of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Walter H LangDepartment of Chemical Biology & Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Ryan P KempenDepartment of Chemical Biology & Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Kumari SwetaDepartment of Chemical Biology & Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Aaron B TaylorCellular Imaging Shared Resource, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Madeleine B BorgiaDepartment of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Aseem Z AnsariDepartment of Chemical Biology & Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: aseem.ansari@stjude.org.
Tanja MittagDepartment of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: tanja.mittag@stjude.org.

Funding

Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Shondra Michelle Miller · 1985 to 2026
$166.9M
Synthetic molecules to stimulate the expression of Frataxin to ameliorate Freidreichs AtaxinR01NS108376 · NINDS · UNIVERSITY OF WISCONSIN-MADISON · PI ASEEM Z ANSARI · 2018 to 2026
$3.6M
Dissecting the contributions of phase separation to yeast transcription .R01GM154414 · NIGMS · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI ASEEM Z ANSARI, Tanja Mittag · 2024 to 2026
$1.5M
NCI NIH HHS P30 CA021765NIGMS NIH HHS R01 GM154414NINDS NIH HHS R01 NS108376
6 · The paper itself

Abstract

Phase separation regulates many biological processes, but the role of transcription factor (TF)-mediated condensates in gene regulation is contentious. We used Gcn4, a prototypical budding yeast TF, to assess two competing models for transcription activation, i.e., mediated via soluble complexes or through transcriptional condensates. We find that the ability of Gcn4 to form soluble complexes with coactivator subunit Med15 closely mirrors its propensity to recruit Med15 into condensates. Both properties are predictive of in vivo activity, cautioning against interpretation of mutational data without direct comparisons. Unexpectedly, Gcn4 variants with the highest affinities for Med15 do not function as per expectation. Instead, their lower activities reflect their ability to phase separate with Med15, suggesting that condensate formation tempers their activity. Our results show that TFs can function as soluble complexes as well as condensates, reconciling two seemingly opposing models, with implications for other phase-separating systems.

Indexed as

Basic-Leucine Zipper Transcription FactorsBiomolecular CondensatesMediator ComplexSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsTranscription FactorsGene Expression Regulation, FungalMutationProtein BindingSolubilityTranscriptional ActivationBasic-Leucine Zipper Transcription FactorsGCN4 protein, S cerevisiaeMediator ComplexSaccharomyces cerevisiae ProteinsTranscription Factorsbiomolecular condensatefuzzy complexGCN4gene regulationintrinsically disordered protein regionMED15Mediatormultivalent interactionphase separationtransactivation domain

Identifiers

PMID40614721
PMCPMC12233198

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Registered trials

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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.