MétaCan
Menu
Back to cohort
Record W4410816879 · doi:10.1016/j.molcel.2025.05.008

A disordered linker in the Polycomb protein Polyhomeotic tunes phase separation and oligomerization

2025· article· en· W4410816879 on OpenAlexafffund
Tim M Gemeinhardt, Roshan Mammen Regy, Tien M. Phan, Jyoti Sharma, Olga Senkovich, Andrea Mendiola, Heather J Ledterman, Amy Henrickson, Daniel Lopes, Utkarsh Kapoor, Ashish Bihani, Djamouna Sihou, Young C. Kim, David Jeruzalmi, Borries Demeler, Chongwoo A. Kim, Jeetain Mittal, Nicole J. Francis

Bibliographic record

VenueMolecular Cell · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA Research and Splicing
Canadian institutionsUniversity of LethbridgeMontreal Clinical Research Institute
FundersU.S. Naval Research LaboratoryNational Institute of General Medical SciencesFonds de Recherche du Québec - SantéNatural Sciences and Engineering Research Council of CanadaNational Science FoundationCanadian Institutes of Health ResearchInstitute of GeneticsNational Institutes of HealthCanada Research ChairsOffice of Naval ResearchHigh Performance Research Computing, Texas A and M UniversityCanada Foundation for InnovationWelch FoundationUniversité de Montréal
KeywordsBiologyLinkerCell biologyIntrinsically disordered proteinsPhase (matter)Separation (statistics)BiophysicsPhysicsComputer science

Abstract

fetched live from OpenAlex

Biomolecular condensates are increasingly recognized as key regulators of chromatin organization, yet how their formation and properties arise from protein sequences remains incompletely understood. Cross-species comparisons can reveal both conserved functions and significant evolutionary differences. Here, we integrate in vitro reconstitution, molecular dynamics simulations, and cell-based assays to examine how Drosophila and human variants of Polyhomeotic (Ph)-a subunit of the PRC1 chromatin regulatory complex-drive condensate formation through their sterile alpha motif (SAM) oligomerization domains. We identify divergent interactions between SAM and the disordered linker connecting it to the rest of Ph. These interactions enhance oligomerization and modulate both the formation and properties of reconstituted condensates. Oligomerization influences condensate dynamics but minimally impacts condensate formation. Linker-SAM interactions also affect condensate formation in Drosophila and human cells and growth in Drosophila imaginal discs. Our findings show how evolutionary changes in disordered linkers can fine-tune condensate properties, providing insights into sequence-function relationships.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.013
Threshold uncertainty score0.293

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.006
GPT teacher head0.288
Teacher spread0.283 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations8
Published2025
Admission routes2
Has abstractyes

Explore more

Same venueMolecular CellSame topicRNA Research and SplicingFrench-language works237,207