Evidence map›Paper›PMID 41620421›Full record

ArticleNature communications2026

Repurposing nuclear receptors for ligand-responsive liquid condensate formation and gene regulation.

Erik Rihtar, Tina Fink, Filip Ivanovski, Eva Koplan, Roman Jerala

Erratum issuedAbstract read
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors.

Erik RihtarDepartment of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia.
Tina FinkDepartment of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia.ORCID http://orcid.org/0000-0001-9907-8948
Filip IvanovskiDepartment of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia.ORCID http://orcid.org/0009-0003-0792-8485
Eva KoplanDepartment of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia.
Roman JeralaDepartment of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia. roman.jerala@ki.si.ORCID http://orcid.org/0000-0002-6337-5251

Funding

EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020) 101059842The Slovenian Research and Innovation Agency (ARIS) J3-60061The Slovenian Research and Innovation Agency (ARIS) J7-4493The Slovenian Research and Innovation Agency (ARIS) J7-4640The Slovenian Research and Innovation Agency (ARIS) P4-0176
6 · The paper itself

Abstract

Cells regulate processes through protein interaction networks. Most chemically induced dimerization (CID) systems respond to exogenous molecules, limiting integration with endogenous signaling. Here, we repurpose nuclear receptor (NR) ligand-binding domains (LBDs) and coactivators to develop hormone- or clinically approved drug-responsive CIDs. Using the LBDs of TRβ, VDR, RARγ, ERβ, and GR2 with a TIF2 coactivator peptide, we constructed CIDs responsive to triiodothyronine, vitamin D, retinoic acid, estrogen, cortisol, and their antagonists. These CIDs enable two-input transcriptional switches for gene regulation. Furthermore, we design hormone-responsive liquid-liquid phase-separated (LLPS) condensates that strongly amplify transcription when exceeding a critical interaction threshold. These functional LLPS condensates provide a tunable platform for transcriptional control with up to several hundred-fold activation. Our findings offer an approach for integrating synthetic biology with physiological signaling, advancing applications in gene circuits, biosensing, and therapeutics through ligand-controlled LLPS formation.

Indexed as

DimerizationSynthetic BiologyTranscriptional ActivationTranscription FactorsHEK293 CellsHumansLigandsProtein Interaction MapsLigandsTranscription Factors

Identifiers

PMID41620421
PMCPMC12963375

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.